Pharmacology ea Penile Erection (2001)

  1. K.E. Andersson1

+ Boikarabello ba Mongoli


  1. Lefapha la Clinical Pharmacology, Sepetlele sa Lund University, Lund, Sweden
- Batla Sengoloa sena

inahaneloang

Motheo ke mofuta oa "spinal Reflex" o ka qalisoang ke ho hira bo-ralitaba tsa penile, empa hape le bohloeki ba pono, boiketso le monahano. Reflex e kenyelletsa boits'oaro bo ikemetseng le bo ikhethang 'me e fetoloa ke litšusumetso tse phahameng. Ho fetisitsoe li-transmitter tse 'maloa tse bohareng tse amanang le taolo ea erectile. Dopamine, acetylcholine, nitric oxide (NO), le li-peptide, tse kang oxytocin le adrenocorticotropic / α-melanocyte e tsosang takatso, li bonahala li e-na le karolo ea ho tsamaisa, athe serotonin e kanna ea ba e tsamaisang kapa ea thibelo, mme enkephalin e le inhibitory. Nako le nako, ho lekana pakeng tsa mokonteraka le lintho tse hlasimollang ho laola boemo ba mokokotlo oa mesifa e boreleli ea corpora cavernosa le ho tseba boemo ba tšebetsong ba botoneng. Likonteraka tsa Noradrenaline ka bobeli li Corpus cavernosum le likepe tsa penile ka ho hlohlelletsa α1-bakeng. Neurogenic NO e nkoa e le eona ntho ea bohlokoahali ea boikhathollo ba likepe tsa penile le corpus cavernosum. Karolo ea babuelli ba bang ba lokolloang ho tsoa methapo kapa endothelium ha e so thehiloe. Erectile dysfunction (ED) e ka bakoa ke ho se khonehe ha mesifa ea penile boreleli ho phomola. Ho se khonehe hona ho ka ba le lisosa tse ngata. Leha ho le joalo, bakuli ba nang le ED ba arabela hantle kalafong ea meriana e fumanehang hona joale. Lithethefatsi tse sebelisoang li khona ho nkela karolo e itseng kapa e felletseng, e sa sebetseng hantle ka mokhoa oa tlhaho oa tlhaho. Lithethefatsi tse ngata li na le ketso e tobileng ho tishu ea penile e thusang ho phumula ha mesifa ka bonolo, ho kenyeletsa le prostaglandin E1, HA HO batho ba fanang ka chelete, inhibitors ea phosphodiesterase, le bahanyetsi ba α-adrenoceptor. Li-receptor tsa dopamine libakeng tsa methapo e bohareng tse nkang karolo ho qaleng ha li-erection li reretsoe kalafo ea ED. Apomorphine, e sebelisoang hanyane ka hanyane, ke mofuta oa pele oa litlhare tse joalo


4. Prostanoids.

Lithane tsa human corpus cavernosum li na le bokhoni ba ho kopanya li-prostanoid tse fapaneng mme li na le bokhoni ba ho li kenya kahare (Miller le Morgan, 1994; Andersson le Wagner, 1995; Porst, 1996; Minhas et al., 2000). Ho hlahisoa ha li-prostanoid ho ka fetoloa ka khatello ea moea le ho hatelloa ke hypoxia (Daley et al., 1996a,b). E tsamaisana le li-metabolites tse hlano tsa mantlha tse sebetsang tsa prostanoid: PGD2, PGE2, PGF2cy, PGI2, le thromboxane A2, ho na le lihlopha tse hlano tse kholo tsa li-receptor tse buellang litlamorao tsa tsona, e leng DP, EP, FP, IP, le li-receptor tsa TP. baemeli ba li-cDNA ba kenyelletsa baemeli ka 'ngoe ea li-receptor tsena li kentsoe, ho kenyelletsa le li-subtypes tse' maloa tsa li-receptor tsa EP, tse hlahisitsoeng ka har'a corpus cavernosum ea motho (Moreland et al., 1999b). Li-receptor tsa prostanoid li G-protein le hammoho le litsamaiso tse fapaneng tsa phetiso (Coleman et al., 1994; Pierce et al., 1995;Narumiya et al., 1999).

Karolo ea li-receptor tse fapaneng tsa prostanoid ho penile physiology e ntse e le hole le ho theoa (Khan et al., 1999). Prostanoids e kanna ea ameha ho arohana ha lisele tsa erectile ka PGF2cy le thromboxane A2, li-thromboxane tse susumetsang le li-receptor tsa FP le ho qala phetoho ea phosphoinositide, hammoho le boikhathollong ka PGE1 le PGE2, e hlohlelletsang li-receptor tsa EP (EP2 / EP4) le ho qala keketseho ea khatello ea methapo ea cAMP. TS'OLO1- Khatholoho ea mesifa ea borena ea motho e ile ea khothaletsoa ho amana le ts'ebetso ea KCa liteishene, le hlahisang hyperpolarization (Lee et al., 1999b). Escrig et al. (1999) fumana PGE e pheta-phetoang1 kalafo e ntlafatsa likarabo tsa erectile ho tsitsipano ea methapo mothong ka ratos ka ho laola li-isoforms tsa NOS.

Prostanoids le eona e ka ameha ho thibelleng ho kopanngoa ha liplatelete le khokahano ea lisele tse tšoeu, 'me tlhaiso-leseling ea morao tjena e fana ka maikutlo a hore li-prostanoids le liphetoho tsa kholo-1(TGF-β1) e ka ba le karolo ea ho fetoloa hoa syntla ea collagen le taolong ea li-fibrosis tsa Corpus cavernosum (Moreland et al., 1995).

Palmer et al. (1994) e fumane hore forskolin, e susumetsang ka kotloloho cymbase ea adenylate, e ne e le tšusumetso e matla ea sebopeho sa cAMP se ikhethileng ka har'a lisele tse boreleli tsa mekhatlo ea batho ea mesifa. Litekanyetso tsa "Thsk" forskolin li fumanoe li eketsa tlhahiso ea cAMP haholo ke PGE1, e khothalelitseng phello ea synergistic. Traish et al. (1997a) e netefalitse phello ena ea synergistic ea forskolin le PGE1 ka har'a lisele tsa setho sa "c" savernosum tsa cultured. Ba boetse ba bonts'itse hore ntlafatso ea moloko oa cAMP o hlahisitsoeng ke forskolin e hlahisitsoeng ke PGE1le PGE0 e kopantsoe ke li-receptors tsa EP mme e hlahisoa ke tšebelisano maemong a adenylyl cyclase le G-protein. Forskolin ka bobeli le PGE1 likhakanyo tse phahameng tsa ho tsepamisa mohopolo linthong tse phahameng le tse bolelele ba khatello ea methapo ho lintja ntle le litlamorao tsa systemic (Cahn et al., 1996). Mulhall et al. (1997) ente forskolin ka hloko ho bakuli ba nang le ED ba neng ba hlotsoe ho arabela kalafo e tloaelehileng ea ente mme ba fumana ntlafatso ea erection ho 61% ea linyeoe. Liphetho tsena li fana ka maikutlo a hore hoa khoneha ho ntlafatsa melemo ea likhoebo tsa PGE1, mohlomong le li-vasodilator tse ling ke li-forskolin le li-analog (Laurenza et al., 1992), 'me e ke ke ea qheleloa ka thoko hore sena se ka fana ka maano a macha a kalafo ea pharmacologic ea ED. Mokhoa o mong oa ho ntlafatsa litlamorao tsa PGE1 e kanna ea kopana le bahanyetsi ba α-AR, joalo ka doxazosin (Kaplan et al., 1998).

5. ATP le Adenosine.

ATP le purines tse ling li bonts'itsoe li fokotsa tsitsipano ea basal le tsitsinyeho ea matla a phenylephrine litokisetsong tse arohaneng tsa bo-rabi Corpus cavernosum (Tong et al., 1992; Wu et al., 1993). Ho ile ha fanoa ka maikutlo a hore ATP ke phetisetso ea NANC ho cosora cavernosa, le hore phetisetso ea purinergic e ka ba karolo ea bohlokoa e kenyelletsang ho qaliseng le ho hlokeng tokiso ea penile (Tong et al., 1992). Leha ho le joalo, ha ho le e 'ngoe ea li-purine tse lekiloeng e ileng ea nolofalletsa kapa ea sitisa karabelo ea mesifa e boreleli ea ts'usumetso ho ts'usumetso ea lebaleng la motlakase, ka hona karolo ea bona e kanna ea fetoha mohopolong oa sebopeho eseng joalo ka li-neurotransmitters (Wu et al., 1993). ATP e kentse kahare ho lintja ka mokhoa o makatsang ea fumaneha hore e hlahisa keketseho ea khatello ea maqhubu le ho chesa (Takahashi et al., 1992a). Tšusumetso ena, e neng e sa angoe ke atropine le hexamethonium, e ka fumaneha ntle le liphetoho likhatellong tsa mali. Ntle le moo, adenosine e hlahisitse tsoelo-pele e felletseng mabapi le taolo e ntle ea litaba (Takahashi et al., 1992b).

Ts'ebetso ea boikhathollo ea ATP e kanna ea arolelanoa ka ho sebelisana ha eona le li-receptor tsa ATP, kapa ka adenosine e hlahisoang ke ho phatloha ho matla ha mokokotlo oa ATP. Adenosine o ile a khothaletsoa ho nka khato ka ho susumetsa li-receptors tsa A2a subtype (Mantelli et al., 1995). Filippi et al. (1999) e fumane hore ATP e sebetsa e le moemeli ea matla le ea ikemetseng oa boikhathollo ba motho le bo-rabi Corpus cavernosum. Ba boetse ba bonts'a hore sephetho sa ATP se ne se bakoa ke ho senyeha ha metabolic ea ATP ho adenosine empa hape e ne e le ka lebaka la tšusumetso e tobileng ea li-receptor tsa P2, tse neng li bonahala li fapane hole le li-receptor tsa khale tsa P2Yand P2X.Shalev et al. (1999) e bonts'itse hore likhoele tsa likhoebo tsa batho li ka khutlisoa ka ho ts'oaroa ha li-purinoceptors tsa P2Y ka ho lokolloa ha MONA. Phomolo ena e kopantsoe ke mochine o its'etleha ka endothelium. Ba khothalelitse hore li-purines li ka ameha molemong oa tlhaho ea tlhaho ho motho. Leha ho le joalo, likarolo tsa ATP kapa adenosine mekhoeng ea ho ikatisa li ntse li lokela ho theha.

6. Mathata a mang.

a. Adrenomedullin le Calcitonin Gene e amanang le Peptide.

Adrenomedullin, e 'nileng ea khothalletsoa ho sebetsa e le khatello ea methapo ea methapo e tsamaisang li-cellular, e na le li-amino acid tsa 52 mme e na le sebopeho se ts'oanang le peptide ea calcitonin-gene-gene (CGRP) (Kitamura et al., 1993). Ho kenella ka mokhoa o hlakileng likatseng, adrenomedullin e bakile khatello e eketsehileng ea maqhubu le ho bolelele ba penile (Champion et al., 1997a-c). Kaha likarabo tsa erectile ho adrenomedullin kapa CGRP li ne li sa angoe ke NO synthase inhibition le l-NAME kapa ke KATP sethala sa inhibition le glibenclamide, ho ile ha fanoa ka maikutlo a hore NO kapa KATP liteishene li ne li sa ameha karabong. Likarabo ho CGRP li ile tsa fokotsoa ke CGRP antagonist CGRP (8-37) ho litekanyetso li se na litlamorao ho karabelo ea adrenomedullin, ho fana ka maikutlo a hore li-peptide li sebelitse li-receptors tse fapaneng. Adrenomedullin le CGRP ba theole khatello ea mali maling a phahameng ka ho fetisisa a sebelisitsoeng. CGRP e kanna ea ba molemo kalafong ea ED (Stief et al., 1990). Leha ho le joalo, hore na adrenomedullin e ka sebelisoa kapa che kapa e na le melemo ho feta CGRP e ntse e lokela ho theha. Ntho e fokotsang basebeletsi ka bobeli ke hore ba tlameha ho kenngoa ka sekhahla.

b. Nociceptin.

Nociceptin ke 17-amino acid peptide e arolelanang thuto ea tlhaho ea lelapa le lelapa la dynorphin la li-peptide. E fapana le li-peptide tse ling tsa opioid ka ho se be le NH2Masala a morao-rao, a bohlokoa bakeng sa tšebetso ho μ, δ, le κ opioid receptors (Henderson le McK Night, 1997; Calo et al., 2000). Setlhare sena ke "ligo endo native" ea "ana" ea likhutsana tse amohelang mefuta e fapaneng ea lihlahisoa: Clone ea motho e bitsoa ORL1. Ts'ebetso ea eona ha e theoe; e kanna ea ameha ho hyperalgesia kapa analgesia (Henderson le McK Night, 1997).

Champion et al. (1997a) Ha ke bapisa likarabo tsa erectile le li-nociceptin tse tsoang ka mokhoa o hlakileng le tse kopantsoeng tse tharo tsa joala, VIP, adrenomedullin, le mofani oa NO likatseng. Nociceptin e lekantsoeng ea 0.3 ho 3 nM e phahamisitse tekanyo e amanang le tekanyo ea khatello ea maikutlo le bolelele ba penile ha bo bapisoa le motsoako oa lithethefatsi tse tharo, empa nako ea karabelo e ne e khuts'oane. Hore na nociceptin e kenella mekhoeng ea erectile le hore na receptor ea ORL1 e ka ba sepheo sa ts'ebetso ea lithethefatsi e ntlafatsang erectile e ntse e lokela ho theha.

C. Ts'usumetso ea Khokahano

1. Elektroniki.

Leha mekhoa e fapaneng ea li-ion e fumanoe liseleng tsa mesifa tse boreleli tsa corpus cavernosum (Kreste et al., 1993; Noack le Noack, 1997; Kreste, 2000), ho bile le lipatlisiso tse nyane tsa motlakase tsa ho hlophisoa ha mesifa ea borena ka botlalo. Leha ho le joalo, ts'ebetso ea motlakase ea corpus cavernosum ea motho ka vivo joalo ka ha e senotsoe ke lithuto tsa electromyographic li hokahanngoa hantle, 'me lisele tsa mesifa tse boreleli li sebetsa joalo ka tumellano e sebetsang (Andersson le Wagner, 1995). Karolong e haufi ea "rat Corpus spongiosum" (penile bulb), Hashitani (2000) e bonts'itse bokhoni ba ho ikatisa molemong oa karolo e ka hare ea mesifa. Ka lehlakoreng le leng, ha ho na lintho tse ka bakang lintho tse ka hlahisoang ke lipatlisiso tsa motlakase tsa lisele tsa mesifa ea setho se secha sa setho sa "cosvern" savernosum.Kreste et al., 1993). Haeba sena se nepahetse bakeng sa lisele tse vivo, e hloka hore ho sebelisoe mokhoa o mong oa ho pharalla. Mochine o joalo o ka fanoa ke likheo tsa likheo.

2. Likarolo tsa likheo.

Joalokaha e thathamisitsoe ke Kreste (2000), phetisetso ea matšoao mesifa e boreleli ea tšebetso ke ketsahalo ea marang-rang ho feta ts'ebetso e bonolo ea ts'ebetso ea "cascade" ea 'mele kapa tsela tseleng e le' ngoe. Likamano tse kopaneng li ka kenya letsoho ho fetoleng molumo oa mesifa o boreleli, 'me ka hona, bokhoni ba erectile, le puisano pakeng tsa mabatooa li ka fa k'hamphani matla a "polokeho" kapa bokhoni ba likarabo / teka-tekano ea likarabo tsa erectile.

Lisebelisoa tsa likamano tsa botona le botšehali li theha lelapa la mofuta oa ion mocha ka har'a mesifa e boreleli ea koporasi. Diyuniti tse bopang pore li etsoa ke hexamers of connexin. Connexin43 ke protheine e tsebahalang ea likheo e fumanehang ho myocyte tse kopane (Campos de Carvalho et al., 1993; Moreno et al., 1993; Kreste, 1995; Brink et al., 1996; Kreste et al., 1996; Serels et al., 1998; Kreste le Brink, 1999). Likarolo tsa likamano tsa likamano tsa likamano tsa likamano tsa botona le botšehali li bonts'a likhokahano tsa liteishene tse kopaneng moo mocha o mong le o mong o thehoang ke kopane, sebakeng se ka ntle sa li-hemichannels kapa li-connexons tse peli, e 'ngoe e fanoang ke sele ka' ngoe ea karolo e haufi. Maqhubu a likonopo tsena ka bomong (ke hore, makholo ho ea ho a likete) a kopaneng liseleng tse haufi tsa sele a etsa motheo oa lipalo tse kopaneng tse atisang ho bonoa, empa eseng kamehla, li bonoang pakeng tsa mesifa e boreleli ea mesifa. Sebetsa se sebetsang sa likarolo tsena ke hore lisele tsa mesifa tse boreleli li sebetse joaloka netweke (Kreste, 2000).

3. Khokahano ea Signal.

Ho hokahanya tšebetso har'a lisele tsa mesifa tse boreleli ke ntho ea bohlokoa bakeng sa ts'ebetso e tloaelehileng ea erectile. Tsamaiso ea methapo ea kutlo e bapala karolo ea bohlokoa molemong ona ka ho fana ka phepelo e kholo ea neuralgenible ho botoneng. Botebo, ho hasoa le likarolo tsa litsela tse fapaneng tsa neuroeffector ha li utloisisoe ka botlalo, 'me ha e le hantle, li ka fapana haholo pakeng tsa batho ba bang le nako e fetang ea motho a le mong. Mohlala, ts'ebetso ea likarolo tse fapaneng tsa tsamaiso ea methapo ea kutlo e fapana haholo nakong ea kemaro, ho senyeha le ho fifala (Becker et al., 2000c). Ha ho le joalo, ho ntse ho hlaka hore karolo ea tsamaiso ea methapo e ikemetseng ts'ebetsong e tloaelehileng ea penile e lokela ho hokahanngoa le phenotype le tšebetso ea li-myocyte tse kopanetsoeng le tsa maemo a holimo. Ka mantsoe a mang, sekhahla sa ho thunya ha tsamaiso ea methapo ea kutlo, ho hlaseloa ha myocyte le mekhoa ea phetisetso ea maqhubu le boholo ba puisano ea sele le sele pakeng tsa lisele tsa mesifa tse tsamaeang hantle li tlameha ho hokahanngoa ka hloko ho netefatsa ts'ebetso e tloaelehileng ea erectile.

Ho khothalelitsoe mokhoa o joalo oa ho hokahanya likarabo tsa lithane (Kreste et al., 1993, 1997; Kreste, 1997) mme e bitswa "Sylimial Tissue Triad". Melao-motheo e laolang tšebelisano ea likarabo tsa mesifa ea botsitso tse fumanehang maemong a mararo: 1) lets'oao, ts'ebetso e otlolohileng ea karolo ea lisele tse boreleli tsa mesifa ke man byosa a pele; ke hore, li-neurotransmitters, li-neurohumors, kapa lihormone, jj.; 2) phatlalatso ea phatlalatso, phatlalatso ea hajoale ea electrotonic le ho kenella ha methapo ea limolek'hule tse amanang le molaetsa oa bobeli oa molaetsa: le 3) phetiso ea matšoao, ho kenella ka har'a maseli a boreleli a tsamaisanang le ts'ebetso ea li-protein tsa transducer G, joalo ka, man messengersosa a bobeli le a boraro, joalo-joalo (Kreste et al., 1993; Kreste, 1997).

D. Khokahano e Ikhethileng

1. Ts'ebeliso ea Ionic.

Ho ajoa ha li-ion hohle ka har'a membrane ea mesifa e boreleli ea mesifa ho bohlokoa kutlwisisong ea ts'ebetso ea mocha oa ion. Ka kopanelo le ho phomola bokhoni ba membrane ea sele ea boreleli ea mesifa, phepelo ena e fihlela qeto ea tataiso ea phallo ea ion nakong ea ho buloa ha mocha ofe kapa ofe oa ion. Li-grionents tsena tsa ionic li lula li bolokiloe ke lipompo tsa ion le li-pacransporters tse sebetsang, 'me li bohlokoa ka ho tebileng tšebetsong e tloaelehileng ea sele ea mesifa e boreleli.

2. K+ Liteshi.

Bonyane tse 'ne tse fapaneng K+ maqhubu a metsi a hlalositsoe ka har'a mesifa ea botsamaisi ba motho (Kreste, 2000): 1) maxi-sens e nang le calcium (ke hore, KCa) seteishene; 2) seterata sa K se laoloang ka metabolikiATP); 3) mocha o liehang ho iphetetsa oa K (joalo ka, KDR); le 4) "A" -type K ea hajoale. KCa mocha le KATP mocha (bona Baukrowitz le Fakler, 2000) li tsebahalitsoe hantle 'me mohlomong li sebetsa hantle ho feta' meleng.

Kabo ea K+ likarolong tsohle tsa mokokotlo oa mesifa e netefatsang hore ho buloa ha lits'ebetso tsa potasiamo ho tla lebisa ho motlakase oa K+ ho tsoa seleng e boreleli ea mesifa, ho theoha le li-gradient tsa bona tsa motlakase. Ho sisinyeha ha tefiso e ntle seleng ho hlahisa hyperpolarization le phello e thibelang transmembrane Ca2+ flux ka liteishene tsa calcium tse itšetlehileng ka matla.

a. KCa Seteishene.

Kanete e nang le "calcium" e na le "calcium" e tsebahala haholo ka mesifa e boreleli ea motho le ea ratWang et al., 2000). KCa Channel MRNA le protheine li fumanoe liseleng tse peli tse ikemetseng tsa batho ba sebetsang le liseleng tsa mokokotlo tse boreleli tsa "Kreste et al., 1999). E lumellana le lipatlisiso tse joalo, ts'ebetso e le 'ngoe ea boits'oaro (≈180 pS), mabili a phallang ka ntle ka seleng, leqhubu la matla a khoheli le calcium.Ca seteishene se ts'oana ha se bapisoa le data e bokelletsoeng ka mahlale a patch clamp ho li-myocyte tse bonolo tsa mekhatlo e sebetsanang le liteko tse tšoanang le tsa lisele tsa mesifa tse bobebe tsa nakoana tsa mokhatlo (bona Fan et al., 1995; Lee et al., 1999a,b).

KCa mocha o bonahala e le sebaka sa bohlokoa se kopanyang ho fetoleng boemo ba tšebetso ea mesifa e boreleli. Ts'ebetso ea mocha ona e eketseha kamora ho kenngwa tšebetsong ha cellular ea tsela ea cAMP ka 8-Br-cAMP kapa PGE1 (Lee et al., 1999a) kapa tsela ea cGMP ke 8-Br-cGMP (Wang et al., 2000). Ho bonahala ho hlakile hore litsela tse peli tse sebetsang hantle haholo tsa 'mele oa mora oa bobeli li sebetsa ho fetolela modumo o hlophisitsoeng oa mesifa (ke hore, boikhathollo bo phahameng), bonyane ka karolo, ka ts'ebetso ea K.Ca seterahlana subtype. Hyperpolarization e hlahisitseng eona, e kopantsoe le ho fokotseha ha "transmembrane" calcium flux ka litselana tsa calcium tsa mofuta oa L (ka tlase), 'me qetellong, ho phomola mesifa e boreleli.

b. KATP Seteishene.

Metsoako ea Bophirimela e metsu e ikhethileng ea lithane, le immunocytochemistry ea lisele tse boreleli tsa mekhatlo e hlophisitsoeng, e sebelisa li-antibodies ho KATPseteishene, ba ngotse boteng ba KATPprotein protein (Kreste et al., 1999). Tumellanong le lipatlisiso tsena, liphuputso tse 'maloa li tlaleha hore li-modulators tsa K, batseteli ba chesehang ba KATPmocha-tlase, o etsa hore ho be le phomolo e itšetlehileng ka khatello ea kelello ea mesifa e ikhethileng ea mothoAndersson le Wagner, 1995). Liteko tsa morao-rao tse mabapi le lisele tsa mesifa tse kopaneng tsa tšebetso tsa mesifa li hatisitse boteng ba mefuta e 'meli e ikhethileng ea ATP+ maqhubu a lisele tsa mesifa tsa mesifa tse bopehileng le tse nchafalitsoeng.Lee et al., 1999a). E lumellana le se bonoang seteisheneng se le seng, lithuto tsohle tsa cell cell patch li tlalehile keketseho e kholo ea glibenclamide e hlokahallang seleng eohle kantle K+ maqhubu a boteng ba modithareng oa K Channel module levcromakalim (bona Lee et al., 1999a). Lintlha tsena, ho tloha molek'huleng, ho ea ka liseleng le liseleng kaofela, li hlakisa boteng le botebo ba 'mele oa KATP Channel subtype (s) ho feto-fetoha ea molumo oa lentsoe oa mesifa ea batho.

3. L-Type Voltage-Dependent Calcium Channels.

Kabo ea li-ion tsa calcium ka hohle ho sebopeho sa sele ea mesifa e boreleli e tiisa hore ho buloa ha liteishene tsa khalsiamo ho tla lebisa ho kenella hoa li-ion tsa calcium ka seleng ea motsamao o boreleli oa motlakase ho theosa mela ea bona ea motlakase. Ho sisinyeha ha tefiso e ntle seleng ea boreleli ea mesifa ho na le phello e fapaneng le motsamao oa K+ ka ntle ho sele, ka hona, e tla lebisa ho depolarization. Boithuto bo 'maloa bo ngotse bohlokoa ba tsoelo-pele ea "transmembrane calcium" e ngata ka Lithaere tsa calcium tse itšetlehileng ka calcium ho fihlela tumellano e tsitsitseng ea mesifa e boreleli ea k'homphieutha (Fovaeus et al., 1987; Kreste et al., 1989, 1990, 1991, 1992a,b). Ho bonahala ho na le tlaleho e le 'ngoe feela e phatlalalitsoeng ea ka hare Ca2+ maqhubu a mesifa e boreleli ea khoebo a sebelisa mekhoa e otlolohileng ea patch clamp (Noack le Noack, 1997). Leha ho le joalo, boholo ba tlhaiso-leseling e qobelloang haholo mabapi le karolo ea liteishene tsa khalori molemong oa ho fetola molumo oa mesifa ea batho ka botsitso e se e thehiloe ka ho sebelisa li-microscopy tsa li-digital imaging tsa Fura-2-li-loaded cultured corporate smooth mes cell. Lithuto tsena li fane ka bopaki bo matla bakeng sa ho ba teng le botebo ba 'mele ba transmembrane calcium flux ka seterata sa calcium se itšetlehileng ka calcium ha se arabela ts'ebetsong ea selefouno ka ET-1 (ETA / Breceptor subtype) le phenylephrine (α1-drenergic receptor subtype (Kreste et al., 1992b; Zhao le Kreste, 1995; Staerman et al., 1997).

4. Manane a Chloride.

Tlatsetso ea liteishene tsa chloride / maqhubu ho feto-fetohang ha molumo oa 'mele oa batho ka tsela e boreleli ha e utloisisehe hantle ho feta ea lits'ebetso tse ling tsa ion. Leha tlhahlobo e thata ea Cl- liteishene li sitisoa ke ho haella ha li-block blockers tse khethiloeng kannete, ho ntse ho na le bopaki bo matla ba ho ba teng ha bonyane ba li-subtypes tse peli- Litsela tsa myocyte tse kopanetsoeng (Kreste et al., 1993), khalsiamo e le 'ngoe ebile e tebile. Mofuta oa calcium o nang le calcium- Channel e na le monyetla o fokolang haholo o bulehileng, e etsang hore tlhahlobo ea bohlokoa ba eona ea 'mele e be mosebetsi o boima. Cl e tsotellang lintho tse ngata- seteishene se kanna sa fana ka mokhoa oa bohlokoa oa "servo" bakeng sa ho lokisa bolelele ba sele ea boreleli ea sefahleho ha ho e-na le li-gradients tse fapaneng tsa hydrostatic, kapa ho feta, nakong ea liphetoho tse potlakileng tsa khampani tse etsahalang nakong ea liphetoho lipakeng tsa phallo ea mali ho ea le ho tsoa penis nakong ea e tloaelehileng ea penile erection le detumescenceFan et al., 1999).

5. Mechine ea Contractile.

a. Konteraka.

Liphetoho ho sarcoplasmic Ca2+mahloriso, 'me ka hona maemong a bokhachane ba sele e boreleli ea mesifa, a ka hlaha ka kapa a sena liphetoho ka bokhoni ba membrane (Somlyo le Somlyo, 1994; Stief et al., 1997). Liphetoho tse ka bakoang ke liphetoho kapa liphetoho tsa nako e telele kamoreng ea phomolo e phomotsang li senya matla a kahare, ka hona, li bula mofuta oa L-mofuta oa mofuta oa C2+ menyetla (Kuriyama et al., 1998). Kahoo, Ca2+ e kenella ka har'a sarcoplasm e tsamaisoang ke gradient ea mahloriso le e tsitsitseng. Liphetoho ho bokhoni ba membrane li ka boela tsa susumetsoa ke liteishene tsa membrane ntle le Ca2+ dikanale. Ho buloa ha K+ liteishene (bona kaholimo) li ka hlahisa hyperpolarization ea membrane ea sele. Hyperpolarization ena e etsa hore menyetla ea calcium ea mofuta oa L e qale ho fella ka hore Ca e fokotsehe2+ tšusumetso le boikhathollo bo latelang ba mesifa.

Mekhoa e meholo e kenyellelitsoeng lipakeng tsa mesifa e boreleli, e sa amaneng le liphetoho liphoofolong tsa membrane, ke tokollo ea IP3 le molao oa tsamaiso ea Ca2+ kutloelo-bohloko. Mehato ka bobeli e ka ba ea bohlokoa bakeng sa ts'ebetso ea mesifa e boreleli ea koporasi. Mabapi le bohlasoa ba bohlokoa ba 'mele ba phosphatidylinositol, li-agonists tse ngata (mohlala, α1-AR agonists, ACh, angiotensin, vasopressin) e tlama ho li-receptor tse ikhethileng tsa membrane tse kopantsoeng le phospholipase C e ikhethang ea phospholipase C ka liprotheine tse tlamang tsa GTP. Phospholipase C ebe hydrolyzes phosphatidylinositol 4,5-biphosphate ho 1,2-diacylglycerol (sena se kenya protheine kinase C) le IP3. IP e qhibilihang ka metsi3 e tlama ho receptor ea eona e ikhethileng (Berridge le Irvine, 1984; Ferris le Snyder, 1992) ka membrane ea sarcoplasmic reticulum (compracellular complication ea Ca2+ polokelo), ka ho etsa joalo e bula Ca2+ mocha. Ho tloha ka Ca2+ mahloriso ka har'a sarcoplasmic reticulum e ka ba 1 mM, Ca2+ ka hona e khanneloa ka har'a sarcoplasm ke mokokotlo oa mahloriso, o etsang hore mesifa e boreleli e thelle. Keketseho ena ea sarcoplasmic Ca2+mahloriso a ka etsa hore ho be le Ca e ikhethang2+mocha oa ho lokolla oa sarcoplasmic reticulum (ke hore, mohlomong seterata se sebetsang sa ryanodine), e lebisang keketseho e 'ngoe Ca2+ mahlaseli a mesifa ea sarcoplasm (Somlyo le Somlyo, 1994; Karaki et al., 1997).

Joalo ka mesifa e tsitsitseng, boholo ba lisebelisoa tsa mahala tsa Ca2+ ke senotlolo sa taolo ea molumo o bonolo oa mesifa. Naheng ea ho phomola, boemo ba sarcoplasmic mahala Ca2+ e lekana le ≈100 nM, athe mokelikeli oa kantle ho metsi o boemong ba Ca2+ e maemong a 1.5 ho 2 mM. Gradient ena ea 10,000-fold e lula e bolokiloe ke cell membrane Ca2+ pompo le Na+/ Ca2+ exchanger. Keketseho e nyane haholo maemong a mahala a sarcoplasmic Ca2+ ka lebaka la 3 ho 5 ho 550 ho 700 nM ebe e tsosa myosin phosphorylation (bona ka tlase) le tumellano e latelang ea mesifa.

Ka seleng e boreleli ea mesifa, Ca2+ tlama le ho boloka khalase, e fapaneng le mesifa e tsitsitseng, moo Ca2+i tlama le protheine e nyane e amanang le "protopane" (troponin)Chacko le Longhurst, 1994;Karaki et al., 1997). K'hamphani ea calcium-utulivuodulin e kenya tšebetsong myosin light chain kinase (MLCK) ka ho tloaelana le motsoako o matla oa enzyme. MLCK e sebetsang e kenya letsoho phosphorylation ea lebone la taolo e laolang subunits ea myosin (MLC)20). Phosphorylated MLC20 e sebetsa myosin ATPase, ka tsela ena e tsosang lihloho tsa myosin (marokho-a-sefapano) tse tsamaeang le lipina tsa "actin", tse hlahisang mesifa e boreleli. Phokotseho ea maemo a makatsang a Ca2+ e etsa hore ho se kopane le mochine oa calcium-calmodulin MLCK, o lebisang ho putlosphorylation ea MLC20 ka phofo ea myosin light phosphatase le phomolong ea mesifa e boreleli (Somlyo le Somlyo, 1994; Karaki et al., 1997). Sebaka se ikhethileng sa nako e telele sa ts'ebeliso ea maqhubu le tšebeliso ea motlakase o fokotsang matla le tšebeliso e tlase ea matla (ATP) se bitsoa a naha. Mokhoa oa naha ena o sebelisang matla a mangata le matla a tlase ha o tsejoe.

Mesifa ea corpus cavernosum e boreleli, e fapaneng le mesifa e boreleli haholo, e qeta nako ea eona e le kontinenteng, ho ile ha fumanoa sebopeho sa myosin se neng se le pakeng tsa aorta le lesapo le boreleli la bladder, leo ka kakaretso le bonts'ang litšobotsi tse kang tonic- le phasic-like (Di Santo et al., 1998), ka ho latellana.

Ka mesifa e boreleli, matla / Ca2+ Karolelano ea lintho ha e tšoane, 'me ho latela likarolo tse itseng tsa ts'ebetso. Mohlala, baetsi ba li-agonists ba α-AR ba susumetsa matla a phahameng / Ca2+ karo-karolelano ea litšenyehelo ho feta ha keketseho e tlisoang ke depolarisation (ke hore, KCl) ho intracellular Ca2+, e fana ka maikutlo a phello ea "khalsiamo e khahlisang" litsebi tsa kelello. Ntle le moo, ho bontšitsoe hore ho sarcoplasmic Ca e sa feleng2+ boemo, ho fokotseha ha matla ("calcium desensitization") ho ka bonoa. Kameho ea li-agonists tse nang le calcium e khahlisoa ke liprotheine tse tlamang tsa GTP tse hlahisang protheine kinase C kapa arachidonic acid e le man messengersosa a bobeli (Karaki et al., 1997; Kuriyama et al., 1998). Mochine o moholo oa Ca2+ sensitization of boreleli mesifa contraction ke ka thibelo ea boreleli mesifa myosin phosphatase, ka tsela eo, eketseha MLC20 phosphorylation ke basal level of MLCK. Theosos phosphorylation e hlahisoang ke mesifa le ho ts'oaroa ke mesifa e latelang ea mesifa ka hona e etsahala ntle le phetoho ho sarcoplasmic Ca2+ mahloriso. Ca2+ sensitization ke tsela ea Rho-A / Rho-kinase e kenya letsoho karolong ea botoneng ea ts'ebetso ea agonist e kentsoeng ke mesifa e boreleli, mme ts'ebetso e atileng ea ts'ebetso ea myosin ka mochine ona e ka bapala karolo ea mafu a itseng (Somlyo le Somlyo, 2000). Tsela ena e nang le calcium ea Rho-A / Rho-kinase e ka boela ea bapala karolo ea ho ts'oaroa ha li-vasoconstriction tsa Cavernosal ho boloka bohloka ba penile. Rho-kinase e tsejoa ho thibela phofo ea myosin light chain phosphatase le ho ts'oara ka kotloloho phosphorylate myosin light chain, ka ho felletseng e lebisang ho eketseheng ha netiti le ts'ebetso ea mokoloto oa selefounu. Le ha protheine ea Rho-kinase le mRNA li fumanoe liseleng tsa ho hlapela, karolo ea Rho-kinase taolong ea molumo oa molumo oa cavernosal ha e tsejoe. U sebelisa mohanyetsi oa Rho-kinase Y-27632, Chitaley et al. (2001) a lekola karolo ea Rho-kinase moloreng oa cavernosal, a ipapisitse le khopolo ea hore ho ts'oarana ha Rho-kinase ho fella ka khatello e eketsehang ea Corpus cavernosum, ho qala karabelo ea erectile ka boikemelo ba NO. Ba fumane hore Rho-kinase antagonism e hlohlelletsa pente ea motho ea ikemetseng ka ntle ho NO mme ba fana ka tlhahiso ea hore molao-motheo ona e ka ba mokhoa o mong o ka sebelisang kalafo ea ED (Chitaley et al., 2001).

b. Phomolo.

Joalo ka mesifa e meng e boreleli, boikhathollo ba mesifa bo boreleli bo kenella hare ka tsamaiso ea methapo ea methapo ea methapo ea methapo. E sebelisa li-receptor tse khethehileng, mohlala, β-AR, litsebi tsa maemo a holimo tsa bophelo li etsa hore ho be le cyclase e ikopantseng ea membrane, e hlahisang cAMP. cAMP ebe e kenya protheine kinase A (kapa cAK), 'me, ho isa tekanyong e nyane, protheine kinase G (kapa cGK). Atgency natriuretic factor (ANF) e sebetsa ka GC e tlamelletsoeng membraneLucas et al. 2000), athe HA ho na letho le ntlafatsang sebopeho sa GC se qhibilihang (bona ka holimo); ka bobeli li hlahisa cGMP, e sebetsang ka cGKI, 'me ka tekanyo e tlase, cAK. CGKI e sebetsang le cAK phosphorylate phospholamban, protheine eo ka tloaelo e thibelang Ca2+ pompo ka har'a membrane ea sarcoplasmic reticulum. Ca2+ Pompo e kenngoa ts'ebetsong 'me, ka lebaka leo, boemo ba cytoplasmic Ca ea mahala2+ea fokotseha, e fella ka ho phomola ha mesifa hantle. Ka mokhoa o ts'oanang, protheine ea protheine e kenya tšebetsong cell membrane Ca2+pompo, e lebisang ho sarcoplasmic Ca e fokotsehileng2+ho tsepamisa mohopolo le phomolong e tlang (Somlyo le Somlyo, 1994;Karaki et al., 1997).

IV. Pharmacology ea Litlhare tsa hajoale le tsa Bokamoso

A. Erectile Dysfunction — Lintho tse Kotsi

Hangata, ED e aroloa ka mefuta e mene e fapaneng: psychogenic, vasculogenic kapa organic, neurologic, le endocrinologic. E kanna ea ba iatrogenic mme ea baka litlamorao tsa kalafo tse fapaneng tsa meriana. Ka nako e telele, ho ne ho lumeloa hore lintlha tsa psychogenic li atile haholo. Leha ho le joalo, leha ho le thata ho khetholla lintlha tsa psychogenic le lefu la manyolo, vasculogenic ED e fumanoe e ikarabella ka bakuli ba 75% ea bakuli ba ED (Polelo ea Naha ea Sechaba ea Phatlalatso ea Bophelo bo Botle, 1993).

Ed e ka ba ka lebaka la ho se khonehe ha mesifa ea penile boreleli ho phomola. Ho se khonehe hona ho ka ba le lisosa tse ngata, ho kenyelletsa ho senyeha ha methapo, tšenyo ea endothelial, phetoho ho polelo ea receptor / ts'ebetso, kapa litseleng tsa phetisetso tse kenelletseng boikhathollong le bokhobong ba sele e boreleli ea mesifa. Ka kakaretso, bakuli ba nang le ED ba arabela hantle kalafong ea meriana e fumanehang hona joale. Ho ba sa arabeng kalafo ea pharmacological (10 ho 15% ea bakuli ba nang le ED), ho ka belaelloa phetoho ea likarolo likarolong tsa mochini oa erectile. Mafu a fapa-fapaneng a amanang le ho hloka tsebo a ka fetola mekhoa e laolang molumo o bonolo oa mesifa. Hangata, liphetoho hol-arginine / NO / cGMP tsamaiso ea ameha.

Ho tsofala ke ntho ea bohlokoa ea kotsi ho ED, 'me ho hakanngoa hore 55% ea banna ha e na matla ho lilemo tsa 75 (Kaiser, 1991; Melman le Gingell, 1999; Johannet et al., 2000). Garban et al. (1995) e fumane hore ts'ebetso ea NOS e qhibilihang e fokotsehile haholo litoneng tsa penile ho tsoa ho likhaba tsa senescent. Polelo ea tlase ea NOS mRNA e fumanoe ho likhoto tsa khale ho feta ho likhoto tse nyane (Dahiya et al., 1997). Mohlaleng o mong oa ratoa oa botsofali, palo ea methapo ea methapo e amanang le NOS kahare botoneng e fokotsehile haholo, 'me karabelo ea erectile ho bohareng le ho hlohlellehong hoa fokola (Carrier et al., 1997). Ka 'mutla oa botsofaling, phomolo e itšetlehileng ka corpot cavernosum e ile ea amoheloa; leha ho le joalo, eNOS e ne e laoloa ka bobeli ka vasotine endothelium le mesifa e boreleli ea koporasi (Haas et al., 1998).

Lefu la tsoekere hangata le amahanngoa le ED (Saenz de Tejada le Goldstein, 1988; Melman le Gingell, 1999; Johannes et al., 2000) le mekhoa e holofatsang ea erectile e haelloang ke NOS. Ka corpus cavernosum e ka thoko ho bakuli ba lefu la tsoekere ba sa foleng, ho phomola ho itšetlehileng ka neurogenic le endothelium ho ne ho senyehile (Saenz de Tejada et al., 1989), mme sena se ile sa fumanoa le mebutlong moo lefu la tsoekere le ileng la bakoa ke alloxan (Azadzoi le Saenz de Tejada, 1992). Ketsahalo ea Penile NOS le litaba tsa penile NOS li ile tsa fokotsoa mefuteng ea litekanyetso ea lefu la tsoekere la mofuta oa I le mofuta oa II la lefu la tsoekere ka ED (Vernet et al., 1995). Leha ho le joalo, ho li-rats tsa lefu la tsoekere tsa streptozotocin, "NOS binding e eketsehile (Sullivan et al., 1996), mme ts'ebetso ea NOS ho lithane tsa penile e ne e phahame haholo ho feta lits'ebetsong, leha ho na le ts'oaro e kholo ea boitšoaro ba mating le matšoao a potency erectile (Elabbady et al., 1995). Ho batho, lefu la tsoekere la "lefu la tsoekere" le khothalelitsoe ho amana le litlamorao tsa lihlahisoa tsa pheletso ea glycation kamorao ho sebopeho sa NO (Seftel et al., 1997).

Atherosulinosis le hypercholesterolemia ke lintlha tsa bohlokoa tsa kotsi tse amehang ho ntlafatsoeng ha vasculogenic ED. Hypercholesterolemia e boetse e fumanoe e sitisa phomolo ea methapo ea methapo ea methapo ea methapo ea mali (corpor cavernosum)Azadzoi le Saenz de Tejada, 1991; Azadzoi et al., 1998). Hypercholesterolemia ha ea ka ea ama ts'ebetso ea NOS, empa e sitisitse ts'epahalo ea endothelium, empa eseng neurogenic, boikhathollo ba "tiski" ea corpus cavernosum tiske. Kaha phomolo e itšetlehileng ka endothelium e ntlafalitsoe kamora kalafo lel-arginine, ho ne ho nahanoa hore ho na le sebopeho se sa lekaneng sa NO ka lebaka la khaello ea tlhaiso ea l-arginine ho liphoofolo tsa hypercholesterolemic.

Ka mohlala oa 'mutla oa atherosulinotic ED (Azadzoi le Goldstein, 1992;Azadzoi et al., 1997), ho bontšitsoe hore ischemia e sa foleng ea cortosal ischemia e sa ts'epahalletseng endothelium feela, empa le boikhathollo ba neurogenic corpus cavernosum le mosebetsi oa NOS (Azadzoi et al., 1998). Ho bile le keketseho e eketsehang ea li-ericosor eicosanoids ka har'a corpus cavernosum. lTsamaiso eaArginine e ile ea hloleha ho ntlafatsa boikhathollo ba Corpus cavernosum, bo khothalletsoang hore bo bakoe ke ho sitisoa ke ts'ebetso ea NOS le phokotso ea sebopeho sa NO.

Ho tsuba ke ntho e ka sehloohong e ka etsang hore motho a ts'oenyehe (Mannino et al., 1994). Ho litoeba, ho tsuba ho sa feleng ho bakile khatello ea methapo e ikemetseng ea lilemo le ho tšoaea ho fokotseha hoa ts'ebetso ea penile NOS le dikahare tsa NNOS (Xie et al., 1997). Sena se ne se sa bonahatsoe ke phokotso ea karabelo ea erectile ho ts'ebetso ea methapo ea motlakase kapa ho fokotseha ha penile eNOS.

B. Lithethefatsi bakeng sa Phekolo ea ho fokola hoa mmele oa Erectile

Ho sebelisitsoe lithethefatsi tse fapaneng bakeng sa kalafo ea ED. Khatelo-pele e kholo e entsoe kutloisisong ea rona ea mekhoa ea ts'ebetso ea lithethefatsi le mekhoa ea ho qaptjoa ha penile, 'me hajoale, ho bonahala ho e-na le lebaka le utloahalang la ho aroloa ha meriana e sebelisoang hona joale. Ho khetholla mofuta o joalo oa bohlokoa ho khothalelitsoe keHeaton et al. (1997), eo ho eona lingaka tsa ED li neng li arotsoe ka lihlopha tse hlano tse kholo ka mokhoa oa tsona oa ts'ebetso: I) ba qalang ba bohareng; II) Liphetolo tse qalang; III) maemo a bohareng; IV) maemo a potoloho; le V) tse ling. Lithethefatsi li ka aroloa le ho feta ke mekhoa ea tsamaiso, mohlala.

C. Lithethefatsi bakeng sa Tsamaiso ea Intracavernous

Har'a litlhare tse ngata tse lekiloeng (Jünemann le Alken, 1989;Jünemann, 1992; Gregoire, 1992; Linet le Ogrinc, 1996; Porst, 1996; Bivalacqua et al., 2000; Levy et al., 2000; Lue et al .; 2000), ke ba bararo feela, ba sebelisitsoeng ba le bang kapa ba kopane, ba amoheloe ka bongata le ho tsamaisoa ka nako e telele, e leng papaverine, phentolamine, le PGE1 (alprostadil). Liphihlelo tsa liteko le tsa tliliniki le li-agents tse ling tse 'maloa tse sebelisetsoang kalafo li tšohliloe ka tlase.

1. Papaverine.

Hangata, Papaverine e khethiloe e le phosphodiesterase inhibitor, empa sethethefatsi se na le ts'ebetso e rarahaneng ea ts'ebetso mme se ka nkuoa e le "lithethefatsi tse sebetsang tsa multilevel"Andersson, 1994). Ho thata ho tseba hore na ke mekhoa efe ea ts'ebetso e 'maloa e sebetsang e ka lebelloang ha lithethefatsi li kenngoa ka sekhahla. In vitro, ho bontšitsoe hore papaverine e hlasimolla methapo ea methapo, lisvernous sinusoids le methapo ea penile (Kirkeby et al., 1990). Lintong, Juenemann et al. (1986) e bonts'itse hore papaverine e ne e na le phello e kopantsoeng ea hemodynamic, e fokotsang ho hanyetsa ho kenella ka hare ho arterial le ho eketsa ho hanyetsa ho tsoa ha venous. Phello ea morao, e bontšitsoeng hape ho motho (Delcour et al., 1987), e kanna ea amana le ts'ebetso ke papaverine ea mochini oa veno-occlusive.

Kaha mochini o ka sehloohong oa ts'ebetso ea papaverine ke thibelo e sa sebetseng ea PDE, mme mesebetsi ea mantlha ea PDE ka har'a causosum ea motho e bonahala e le PDE3 le PDE5, li -hibidure tsa PDE tse ka kenang ka liketso liketsong tsena tsa li-isoenzymes, empa tse se nang "litla-morao" tsa litla-morao tsa papaverine , e ka ba mokhoa o mong o khahlisang.

2. α-Adrenoceptor Antagonists.

a. Phentolamine.

Phentolamine ke mohanyetsi oa α-AR oa tlholisano ea nang le tumellano e ts'oanang ea α1- le α2-AR, 'me ke mokhoa oa eona o ka sehloohong oa ts'ebetso. Leha ho le joalo, sethethefatsi se ka thibela li-receptors tsa 5-HT mme sa etsa hore ho lokolloe histamine liseleng tsa methapo. Phentolamine e boetse e bonahala e na le ketso e 'ngoe, mohlomong e kenyelletsang ts'ebetso ea NOS (Traish et al., 1998). Kaha phentolamine nonselectively e thibela li-α-AR, ho ka lebelloa hore ka ho thibela pele ho pele2-ARI, e ne e tla eketsa tokollo ea NA ho tsoa methapong ea adrenergic, ka hona e loants'a ea eona ea morao-rao ea posta1-Khato tse thibelang. Ha ho tsejoe hore na ketso e joalo kapa che e kenyelletsa katleho e lekantsoeng ea phentolamine e fanoang ka bohlale ho hlahisa erection.

Ho lintja, phentolamine e kang papaverine e fokotse ho hanyetsa ho kenella ka hare ho botona. Leha ho le joalo, papaverine, empa eseng phentolamine, e ile ea eketsa ho hanyetsa ha venous outflow (Juenemann et al., 1986). Ho haella ha phello ea venous tsoa ke intracavernous phentolamine le hona ho bontšitsoe ho motho (Wespes et al., 1989).

Ho na le khaello e akaretsang ea tlhaiso-leseling ka pharmacokinetics ea phentolamine. Setlhare se na le katleho e fokotsehileng ha se fanoa ka molomo, mohlomong ka lebaka la metabolism e pharalletseng ea pele. Ho bontšitsoe phapang pakeng tsa plasma half-life (30 min) le nako ea phello (2.5-4 h) e bontšitsoe (Imhof et al., 1975); hore na sena se ka hlahisoa ke metabolites e sebetsang ha e tsejoe. Ha moriana o fanoa ka hloko, serum ea phentolamine e tla fihla sehlohlolong kahara 20 ho isa ho 30 min ebe e theoha ka potlako ho maemo a sa bonahaleng (Hakenberg et al., 1990).

Litlamorao tse atileng haholo tsa phentolamine kamora tsamaiso ea methapo ke methapo ea methapo le orthostatic hypotension le tachycardia. Cardiac arrhythmias le infraime ea myocardial li tlalehiloe, empa tsena ke liketsahalo tse sa tloaelehang haholo. Ka mohopolo, litlamorao tse joalo li ka ba teng le ka mora ts'ebetso ea botsitso, empa ho fihlela joale ha ho bonahale ho le joalo. Kaha ente e le 'ngoe ea intracavernous phentolamine ha e felle ka karabelo e khotsofatsang ea erectile maemong a mangata, lithethefatsi li sebelisoa ka bongata hammoho le papaverine (Zorgniotti le Lefleur, 1985; Jünemann le Alken, 1989) kapa VIP (Gerstenberg et al., 1992).

b. Thymoxamine.

Thymoxamine (moxisylyte) e na le ts'ebetso ea thibelo le e batlang e khetha hofeta ho α1-MAROLO. Ntle le moo, e kanna ea ba le liketso tsa antihistaminic. In vitro, moxisylyte e ntlafalitse litokisetso tsa NA tsa konteraka tsa motho tsa konteraka ea batho (Imagawa et al., 1989) empa e ne e le matla haholo ho feta prazosin le phentolamine.

Hanyane ha ho tsejoe ka pharmacokinetics ea eona, empa kamora ts'ebetso ea tsamaiso, e na le phello ea nako ea 3 ho 4 h. Moxisylyte ke setlhare se fetolang ka potlako metabolite e sebetsang ho plasma (deacetylmoxisylyte). Ho felisoa ha metabolite e sebetsang ho etsahala kaN-demethylation, sulfo-, le glucuroconjugation. TheN-demethylated metabolite e sulfoconjugated feela. Motsoako ke eona tsela e ka sehloohong ea ho chona.Marquer le Bressole, 1998).

Moxisylyte o ile a bonts'oa ho hlahisa sebopeho ha a entetsoa ka sekhukhu (Brindley, 1986), le lithutong tse peli tsa bofofu tse sa boneng, Buvat et al. (1989) e bontšitse hore e mafolofolo ho feta saline empa e sa sebetse ho feta papaverine. Buvat et al. (1989) ho tlalehiloe ka liphihlelo tsa ente e kenelletseng ea moxisylyte ho bakuli ba 170 ba nang le khatello ea matla mme a supa hore moriana ha o qale, empa o nolofalitse, oa bokella ka ho susumetsa ho ruruha hoa nako e telele. Ba boetse ba hatella hore menyetla e ka sehloohong ea moriana oo ke polokeho ea oona. Ke bakuli ba babeli feela ba bakuli ba 170 ba kenyelitseng nako e telele. Buvat et al. (1991), ho bapisa papaverine le moxisylyte, hape ho fumanoe hore moxisylyte o ne a na le tšekamelo e fokolang ea ho hlahisa li-fibrosis tsa khoebo ho feta papaverine (1.3 bapisoa le 32%). Lintlha tse ntle tsa polokeho li ile tsa hatisoa ke Arvis et al. (1996), ea sa tlalehang litlamorao tse mpe ho banna ba 104 ba ileng ba latela bakeng sa likhoeli tsa 11 le ho iketsetsa tsamaiso ea 7507.

Phuputsong e bapisang pakeng tsa moxisylyte le PGE1, Buvat et al. (1996) e bontshitse PGE eo1 e ne e sebetsa haholo ho feta moxisylyte (71 bapisoa le ba arabelang 50%), haholo ho bakuli ba nang le bothata ba khatello ea methapo (96 khahlanong le 46%). Leha ho le joalo, moxisylyte e mamelletsoe hamolemo ho feta PGE1 etsa hore ho be le lintho tse sa khaotseng tse nkang nako e telele hanyane ka hanyane.

Joaloka sethethefatsi se thusang, moxisylyte e kanna ea ba khetho e 'ngoe e loketseng bakeng sa kalafo ea ED. Nts'etsopele e khahlisang ke nitrosylated moxisylyte, e ka sebetsang e le mofani ea kopaneng oa NO le α1-AR antagonist (de Tejada et al., 1999). Lithuto tsa kliniki ka sethethefatsi sena li ntse li fokola ho fihlela joale.

3. Prostaglandin E1 (Alprostadil).

TS'OLO1, ente e kenngoeng ka hloko kapa e sebelisoang intraurethrally, hajoale ke e 'ngoe ea lithethefatsi tse sebelisoang haholo bakeng sa kalafo ea ED (Linet le Ogrinc, 1996; Porst, 1996; Hellstrom et al., 1996; Padma-Nathan et al., 1997), le likarolo tse 'maloa tsa litlamorao tsa eona le tšebeliso ea tliliniki li hlahlojoe (Linet le Ogrinc, 1996; Porst, 1996). Litekong tsa bongaka, 40 ho 70% ea bakuli ba nang le ED ba arabela jekeng ea intracavernosal ea PGE1. Lebaka leo bakuli ba bangata ba sa arabeng ha le tsejoe. Angulo et al. (2000) e arabile likarabo ho PGE1ka har'a mesifa ea borena ea methapo ea kutlo le methapo ea methapo ea kutlo, eo ka bobeli e bontšitseng phapang e kholo ho arabeleng PGE1. Ba fumane khokahano ea karabelo ea in vitro le karabelo ea bongaka erectile mme ba khothaletsa hore liphetho tsa bona li ka hlalosa hore na hobaneng bakuli ba bang ba araba mme ba bang ba sa lokela ho kena PGE e makatsang1.

TS'OLO1 e kenngoa ka har'a lisele tsa penile ho PHE0 (Hatzinger et al., 1995), e sebetsang ka bioloji mme e ka kenya letsoho phello ea PGE1 (Traish et al., 1997a). TS'OLO1 e ka etsa karolo e itseng ka ho thibela tokollo ea NA (Molderings et al., 1992), empa ketso ea mantlha ea PGE1 le PGE0 mohlomong e le ho eketsa ho tsepamisa mohopolo kahare ho cAMP ka har'a lisele tsa mesifa tse boreleli tsa corpus cavernosumPalmer et al., 1994; Lin et al., 1995; Cahn et al., 1996; Traish et al., 1997a).

TS'OLO1 e tsejoa hore e na le litlamorao tse fapaneng tsa meriana. Mohlala, e hlahisa vasodilatation e hlophisehileng, e thibela ho kopana ha liplatelete, 'me e matlafatsa tšebetso ea mala. E sebelisitsoe ka mokhoa o hlophisitsoeng, lithethefatsi li sebelisitsoe tliliniki ho isa tekanyong e lekanyelitsoeng. Hanyane hanyane ho tsejoa ka pharmacokinetics ea eona, empa e na le nako e khuts'oane ea ts'ebetso mme e sebetsa haholo. Hoo e ka bang 70% e kanna ea ts'oaetsoa ka har'a 'mala o le mong.Gloub et al., 1975), e ka 'nang ea hlalosa hore na ke hobaneng ha e baka litla-morao tsa ho potoloha ha e ente ka ho hlaka.

Angulo et al. (2000) e bonts'itse hore motsoako oa PGE1 le S-nitrosoglutathione (SNO-Glu) mesifa e phutholohileng e lula e le bonolo kapa e sa phomole hantle ho PGE1. Ba khothalelitse karabo ea bongaka ho PGE1 e kanna ea fokola ho bakuli ba bang ka lebaka la ho haelloa ke karabelo ea mesifa e bonolo ea Pile1 ha a ntse a boloka bokhoni ba ho phomola ka lebaka la basebeletsi ba sebelisang mekhoa e meng ea boikhathollo. Motsoako oa PGE1 mme SNO-Glu e ne e na le tšebelisano ea synergistic ho hlasimolla mesifa ea penile trabecular boreleli, mme ho ne ho nahanoa hore motsoako o joalo o ka ba le menyetla e meholo ea kalafo kalafong ea monna oa banna.

4. Vasoactive Intestinal Polypeptide.

Joalokaha ho hlalositsoe pejana, karolo ea VIP e le neurotransmitter le / kapa neuromodulator ka botoneng e hlahisitsoe ke bafuputsi ba 'maloa, empa bohlokoa ba eona ea penile erection ha e so theoe (Andersson le Wagner, 1995; Andersson le Stief, 1997). Le ha ho le joalo, ho se khonehe ha VIP ho hlahisa popo ha e kentsoe ka mokhoa o kenang ka kotloloho ka popo (Wagner le Gerstenberg, 1988kapa banna ba se nang matla (Adaikan et al., 1986; Kiely et al., 1989; Roy et al., 1990) e bonts'a hore e ke ke ea ba 'muelli ea ka sehloohong oa NANC oa boikhathollo ba lithane tsa penile erectile.

VIP e bontšitsoe ho hlahisa mefuta e mengata ea litlamorao. Ke vasodilator e nang le matla, e thibelang ts'ebetso ea bokhachane ka mefuta e mengata ea mesifa e boreleli, e tsosa boikemisetso ba pelo le makunutu a mangata a emelang. E susumetsa li-cyclase tsa adenylate le ho theha cyclic AMP (Fahrenkrug, 1993).

Wagner le Gerstenberg (1988) e fumane hore leha e le litekong tse phahameng (60 ug), VIP ha e khone ho kenya letsoho ho kenella ka ente e kenelletseng ho banna ba nang le matla. Ka lehlakoreng le leng, ha e sebelisoa hammoho le tšusumetso ea bonohe kapa e susumetsang, VIP ea maiketsetso e ne e nolofalletsa tloaelo e tloaelehileng.Kiely et al. (1989) ente VIP, papaverine, le motsoako oa lithethefatsi tsena tse nang le phentolamine intracorporeally ho banna ba leshome le metso e 'meli ba nang le matla a ho fapana ha etiology. Ba netefalitse hore VIP feela e haelloa ke ts'usumetso ea maiketsetso a batho. Le ha ho le joalo, hammoho le papaverine, VIP e ile ea hlahisa botsitso ba penile e ts'oanang le e fumanoeng ka papaverine le phentolamine. Gerstenberg et al. (1992) e tsamaisoa ka VIP hammoho le phentolamine ka hloko ho bakuli ba 52 ba nang le ho hloleha ha erectile. Liperesente tse 40 tsa bakuli ba ne ba kile ba fumana kalafo ka papaverine feela kapa ka papaverine le phentolamine. Kamora ho hlohlelletsa ka thobalano, bakuli bohle ba ile ba fumana erection e lekane bakeng sa ho kenella kahare. Bakuli bao ba kileng ba phekoloa ka papaverine kapa papaverine / phentolamine ba boletse hore ketso ea motsoako oa VIP e batla e tšoana le potoloho e tloaelehileng ea likamano. Ha ho na mokuli ea neng a e-na le bokuli ba 'mele, kapa li-fibrosis tsa khoebo, kapa bothata bofe kapa bofe bo bong bo tebileng (Gerstenberg et al., 1992). Liphetho tsena tse ntle li netefalitsoe ke bafuputsi ba bang (McMahon, 1996; Dinsmore le Alderdice, 1998; Sandhu et al., 1999). Kahoo, Sandhu et al. (1999) o fumane hore ho sebelisa ente e ncha ea auto-injection thutong e laoloang habeli ea mahlo moo ho nang le bakuli ba 304 ba nang le psychogenic ED, ba fetang 81% ea bakuli le 76% ea balekane ba tlalehile boleng bo ntlafalitsoeng ba bophelo.

VIP e fuoeng kahare e ka hlahisa hypotension, tachycardia le ho thunya (Palmer et al., 1986; Frase et al., 1987; Krejs, 1988). Leha ho le joalo, karolo ea bophelo ba plasma halofo ea nakoana ea peptide e khuts'oane, e ka kenyelletsang taba ea hore litla-morao tsa li-systemic li na le seoelo ha li tsamaisoa ka hloko (McMahon, 1996; Sandhu et al., 1999). Ketsahalo e mpe e mpe e ne e bonahala e le lerootho sefahlehong.

Ho bonahala eka VIP e sebelisoang ka mokhoa o kopantsoeng le phentolamine e kanna ea ba mofuta o mong oa kalafo e thehiloeng ka botlalo ka papaverine / phentolamine kapa PGE1, empa boiphihlelo bo eketsehileng boa hlokahala ho fana ka tlhahlobo e nepahetseng ea melemo le likotsi tsa motsoako ona.

5. Calcitonin Gene e amanang le Peptide.

Stief et al. (1990)e bonts'itse CGRP ka methapo ea kholo ea motho corpore mme a khothaletsa tšebeliso ea eona ho ED. Meleng ea mali ea motho e tsoang libakeng tse fapaneng, CGRP e tsejoa e le vasodilator e matla. Phello ea eona e kanna ea itšetleha kapa ea ikemela ho vasotine endothelium (Crossman et al., 1987;Persson et al., 1991). Peptide e ile ea nchafatsa mokokotlo oa bovine ka ketso e tobileng liseleng tse boreleli tsa mesifa (Alaranta et al., 1991), e fanang ka maikutlo a hore e ka ba le litlamorao tsa bohlokoa ho penile vasculature.

Ho bakuli, ente ea intracavernosal ea CGRP e bakile keketseho e amanang le lethathamo la phallo ea methapo ea kutlo, ho phomola ha mesifa ka mokhoa o boreleli, phallo ea methapo ea methapo, le likarabo tsa erectile. Motsoako oa CGRP le PGE1 e kanna ea sebetsa ho feta PGE1 ke le mong (Stief et al., 1991b;Djamilian et al., 1993; Truss et al., 1994b).

Joaloka mothehi oa ntlafatso, CGRP e ka ba molemo molemong oa kalafo mme e ka se qheleloe ka thoko e le setlhare se tataisang, se le mong kapa se kopantsoe le lithethefatsi tse ling, empa ho lekola bokhoni ba sona, boiphihlelo bo eketsehileng boa hlokahala.

6. Linsidomine Chlorhydrate.

Hoa utloahala ho nahana hore lithethefatsi tse sebelisoang ke NO li ka ba molemo ho kalafo ea ED. Linsidomine, metabolite e sebetsang ea lithethefatsi tsa antianginal molsidomine, ho lumeloa hore e sebetsa ka tokollo ea nonenzymatic ea NO (Feelisch, 1992; Rosenkranz et al., 1996), eo ka ho susumetsa GC e qhibilihang e eketsa litaba tsa cyclic GMP liseleng tsa mesifa e boreleli ebe e hlahisa phomolo. Linsidomine e boetse e thusa ho kopana le liplatele (Fokotsa 1990), le linaheng tse ling, e ngolisitsoe bakeng sa kalafo ea cosophary vasospasm le coronary angiography. Ho ile ha tlalehoa hore lithethefatsi li na le bophelo ba plasma halofo ea 1 ho isa 2 h (Wildgrube et al., 1986;Rosenkranz et al., 1996).

Linsidomine e fumanoe e le ho phomola hantle litokisetso tsa mmutla le setopo sa motho sa konteraka se entsoeng ke NA kapa ET-1 ka tsela e itšetlehileng ka mahloriso (Holmquist et al., 1992a). Lithutong tsa pele, Stief et al. (1991a, 1992), Le Truss et al. (1994a)o ithutile phello ea linsidomine e kentseng entracorporeally ho bakuli ba se nang matla 'me a fumana hore lithethefatsi li kenya karabelo ka erectile ka ho eketsa ho kenella ha arterial le ho phomola mesifa e boreleli ea cavernous. Ho ne ho se na litla-morao tsa tsamaiso ea lehae kapa ea lehae, 'me ha ho na mokuli ea bileng le tšusumetso ea nako e telele. Liphetho tsena tse ts'episang ha lia tiisoa ke bafuputsi ba bang (Porst, 1993; Wegner et al., 1994). Liteko tsa bongaka tse laoloang ke placebo tse laoloang ke placebo li tlameha ho etsoa ho bona hore na linsidomine ke mofuta o mong oa kalafo o ka sebelisoang ho litlhare tse teng bakeng sa ente ea intracorporal.

Monehi e mong oa NO, sodium nitroprusside (SNP), o fuoe ka mokhoa o makatsang bakeng sa kalafo ea ED, empa ho bontšitsoe hore ha e sebetse (Martinez-Pineiro et al., 1995; Tarhan et al., 1996, 1998) mme e bakile hypotension e kholo. Liphetho tsena tse nyahamisang ho bafani ba NO ha li qobelle hore lithethefatsi tse sebelisoang kel-arginine / NO / GC / cGMP tsela e ka ba e sebetsang bakeng sa kalafo ea ED (bona ka tlase).

D. Lithethefatsi bakeng sa Tsamaiso e sa Ts'oaneng

Lithethefatsi tse ka fanoang ke mefuta e meng ntle le ho intša ka kotloloho li ka ba le melemo e 'maloa kalafong ea ED (Morales et al., 1995;Burnett, 1999; Morales, 2000a). Ka kakaretso ho na le karabelo e phahameng ea placebo (30 ho 50%) ho lithethefatsi tse sa sebetseng ka mokhoa o seng molaong. Ka hona, liteko tse laoloang ke placebo le lisebelisoa tse sebetsang tse sebelisoang ho lekanya karabo li tlamehile ho lekola litlamorao tse lekaneng.

1. Nitrate ea manyolo.

Nitroglycerin le li-nitrate tse ling tsa organic ho lumeloa hore li baka phomolo e boreleli ea mesifa ka ho susumetsa GC e qhibilihang ka tokollo ea enzymatic ea NO (Feelisch, 1992). Ka bobeli nitroglycerin le isosorbide nitrate li fumanoe li thusa ho thelolla marikhoe a ikemetseng a corpus cavernosum (Heaton, 1989).

Tsamaiso ea transdermal ea nitroglycerin e thehiloe hantle kalafong ea angina pectoris. Phello ea hore tšebeliso ea li-nitroglycerin ka botoneng e ka lebisa ho ekeletsong e lekanang bakeng sa thobalano (Tiking le Crawley, 1985) e hlahisitse lipatlisiso tse 'maloa mabapi le ho sebetsa ha mofuta ona oa kalafo oa ED.

Owen et al. (1989) o entse phuputso e sa laoleheng e laoloang habeli ka phello ea mafura a nang le nitroglycerin e sebelisitsoeng botoneng ba bakuli ba se nang matla ba 26 ba nang le tlhahlobo ea matla a tlhaho, a psychogenic, kapa a mofuta o tsoakaneng. Mabapi le placebo, nitroglycerin e ekelitse phello ea penile haholo ho 18 ea bakuli ba 26, mme ho 7 ea bakuli ba 20 e ile ea eketsa phallo ea mali methapong ea methapo ea methapo. Hypotension le hlooho e ne e bonoa ho mokuli a le mong. Litekong tse laoloang ka tšohanyetso tse sa laoloeng, tse sa sebetsanang le maemo, Claes le Bart (1989) e phekotse banna ba se nang matla ba 26 ba nang le patroglycerin patches. Ba hlokometse karabelo e nepahetseng ho nitroglycerin ka ho khutlela tšebetsong e khotsofatsang ea thobalano ho bakuli ba 12 (46%), le ntlafatso e itseng ea erectile ho 9 (35%). Ke 1 feela ea 26 e tlalehileng tsosoloso ea potency e nang le patches ea placebo. Bakuli ba leshome le metso e 'meli ba tlaleha ho ba le hlooho e fokolang ho isa tekanyong nakong ea kalafo ea nitroglycerin.

Litlamorao tsa samente ea nitroglycerin e sebelisitsoeng botoneng le tsona li ile tsa hlahlojoa ho bakuli ba se nang matla ba 10 ke Meyhoff et al. (1992). Ba fumane hore ha ba lekoa ka laboratoring, bakuli bohle ba fumana karabelo erectile. Ha samente e ipusa, potency e ile ea khutlisoa ka tse 'ne, semirigidity e neng e sa lekana bakeng sa thobalano e ile ea bonoa habeli, tumescence ho tse tharo, mme ha ho na phello e le' ngoe. Bakuli ba supileng ba ile ba tletleba ka hlooho. Karabelo e lekaneng ea erectile ho polasetiki e tšoanang ea nitroglycerin e fumanoe ho 5 ea bakuli ba 17 ba lemetseng ea lesapo la mokokotlo (Sønksen le Biering-Sørensen, 1992).

Ho bapisa transdermal nitroglycerin le ente e kenang ea papaverine ho bakuli ba 28 ba nang le lesapo la mokokotlo le ED, Renganathan et al. (1997) e fumane hore 61% e arabetse nitroglycerin le 93% ho papaverine. Bakuli ba robong ba ile ba ba le mathata a amanang le papaverine, athe eona feela phello ea transrermal nitroglycerin e ne e le hlooho e bohloko ea hlooho (21%). Le ha katleho e fokola 'me hlooho e bonahala e le litlamorao tse tloaelehileng, nitroglycerin e ka ba kalafo e sebetsang ho bakuli ba khethiloeng.

2. Phosphodiesterase Inhibitors.

Thel-arginine / NO / GC / cGMP tsela e bonahala e le ea bohlokoa ka ho fetisisa bakeng sa ho qaptjoa ha penile ho mefuta e meng (bona ka holimo), le liphetho tsa morao-rao ka sildenafil, inhibitor e khethiloeng ea PDGXPNUMX e ikhethang, e ts'ehetsa pono e eketsehileng ea hore sena e kanna ea ba molato le ho batho (Boolell et al., 1996a,b). Sildenafil ke makhetlo a 4000 a khethang ho feta PDE5 ho feta PDE3, makhetlo a 70 a ikhethile ho feta PDE5 ho feta PDE4, empa ke 10 feela e khethang ho feta PDE5 ho feta PDE6 (Ballard et al., 1998; Moreland et al., 1998, 1999a). Sildenafil e kenella ka potlako ka mor'a taolo ea molomo (bioavailability 41%) mme e na le plasma halofo ea bophelo ba 3 ho 5 h.

Palo e kholo ea liteko tse laoloang ke placebo, tse sa reroang, tse habeli li bontšitse hore sildenafil e ka ntlafatsa li-erections ho banna ba nang le ED, ho sa tsotelehe hore na sesosa se bakoa ke psychogenic, organic, kapa mabaka a kopaneng (Steers, 1999; Levy et al., 2000). Kaha PDE5 ha e lekanyetsoe botoneng feela, empa e ka fumanoa liseleng tse ling hape, litla-morao tse kang ho ts'oaroa ha nko, dyspepsia, hlooho e opang, sefahleho le sefubeng, 'me letšollo le ka ba teng. Litla-morao tse ka bang teng tsa pelo le pono li hlahisitse lipuisano tsa polokeho. Pheko e phethahetseng ho sildenafil ke ts'ebeliso ea li-nitrate, 'me tse' maloa, empa eseng kaofela, tsa lefu le amanang le ts'ebeliso ea sildenafil li hlahisitsoe ka tšebeliso e tšoanang ea li-nitrate. Leha ho le joalo, ho latela boiphihlelo ho fihlela joale, sildenafil e lokela ho nkuoa e le sethethefatsi se sireletsehileng (Conti et al., 1999;Steers, 1999; Zusman et al., 1999).

Sildenafil e bonahala e le e 'ngoe ea liemahale tse matlafatsang ka ho fetisisa bakeng sa kalafo ea ED. Tekanyo e phahameng ea karabelo le mamello e ntle e e etsa khetho e ntle ea pele ho bakuli bao pele ba neng ba ka nkoa e le likhetho tsa kalafo ea ente.

Joalokaha ho boletsoe pejana, li-inhibitors tse ling tse 'maloa tsa PDE5 tse ikhethileng li se li ntse li tsoela pele ((Meuleman et al., 1999; Giuliano et al., 2000c; Noto et al., 2000; Oh le al., 2000; Rotella et al., 2000; Stark et al., 2000), empa palo ea tlhaiso-leseling ea kliniki e teng.

3. Prostaglandin E1.

Lisebelisoa tsa Vasoactive li ka tsamaisoa ka holimo ho mucosa ea urethral 'me ho ka bonahala li ka kenella kahare ho Corpus spongiosum' me tsa fetisetsoa ho corpora cavernosa. TS'OLO1 (alprostadil) le PGE1/ motsoako oa prazosin o bonts'itsoe ho hlahisa li-erections ho bakuli ba bangata ba nang le "organ" e sa foleng (Peterson et al., 1998). Phuputsong e lebelletsoeng, e nang le mefuta e mengata, thuto e laoloang habeli ea blindbo e laoloang ho bakuli ba 68 ba nang le nako e telele ea ED ea mantlha ka tlhaho (Hellstrom et al., 1996), alprostadil e tsamaisitsoeng ka nako e fetisisang e hlahisitse katoloso e felletseng ea botona ho 75.4%, mme 63.6% ea bakuli ba tlalehile ho kopanela liphate. Litlamorao tse atileng haholo e ne e le bohloko ba penile, bo fumanoang ke 9.1 ho 18.3% ea bakuli ba fumanang alprostadil. Ho ne ho se na likarolo tsa kemolo. Phuputsong e 'ngoe e laoloang ke mahlo sebakeng se habeli ho banna ba 1511 ba nang le ED e sa foleng ka mabaka a fapaneng a tlhaho, 64.9% e bile le thobalano ka katleho ha e nka transurethral alprostadil ha e bapisoa le 18.6% ho placebo (Padma-Nathan et al., 1997). Hape litlamorao tse atileng haholo e ne e le bohloko bo bobe ba penile (10.8%). Liphihlelo tse ntle le tsona li tlalehiloe ke Guay et al. (2000) Ho hlahloba bakuli ba 270 ka morao-rao. Bakeng sa banna ba fumanang ente ea maqeba e kenang e le bothata, boikhethelo ba alprostadil ea intraurethral ke khetho. Bohloko ba penile e lula e le bothata ho bakuli ba bangata.

4. K+ Bannete ba Channel.

Tse 'maloa K+ li-open openers (pinacidil, cromakalim, lemakalim, le nicorandil) li bontšitsoe li sebetsa hantle ho bakeng phomolo ea lisele tse ikhethileng tse tsoang liphoofolong le bathong, le ho hlahisa menyetla ha e kenelletse ka botebo litšoeneng le bathong (Andersson, 1992; Benevides et al., 1999). Leha ho le joalo, ke minoxidil feela, vasodilator ea arteriolar e sebelisoang e le li-antihypertgency agents ho bakuli ba nang le khatello e matla ea mali, ho bonahala eka ho kile ha etsoa liteko ho monna. Minoxidil ke ngaka e sa sebetseng ka har'a vitro empa e tšeloa ka har'a sebete ho molek'hule e sebetsang, minoxidil NO sulfate (McCall et al., 1983). Ho bontšitsoe hore minoxidil sulfate e na le thepa ea K+ senotlolo se bulehileng. Minoxidil e kenelletse hantle, ka bobeli ho tsoa ka mpeng ea mpa le ka transmermally, empa biotransformation ea eona ho metabolite e sebetsang ha e so ka e hlahlojoa ho motho. Setlhare se na le bophelo ba halofo ea plasma ea 3 ho 4 h, empa nako ea litlamorao tsa eona ea methapo ke 24 h kapa e telele haholo.

Ka teko e foufetseng habeli, minoxidil e ile ea fuoa bakuli ba 33 ba nang le neurogenic le / kapa sebopeho sa arterial mme e bapisoa le placebo (li-lubricating gel) le nitroglycerin (2.5 g ea oli ea 10%). Minoxidil e sebelisitsoe ho glans penis e le 1 ml ea tharollo ea 2%. Minoxidil e ne e phahame ho feta "placebo le nitroglycerin" ho eketsa ho ruruha ha penile, mme ho ile ha fanoa ka maikutlo a hore moriana o ka nahanoa bakeng sa kalafo ea nako e telele ea ho se sebetse hoa manyolo (Cavallini, 1991, 1994).

Litlamorao tse kholo tsa lithethefatsi, ha li sebelisoa kalafong ea khatello ea mali, ke ho bolokoa ha metsi le letsoai, litlamorao tsa pelo le pelo ho kenella ts'ebetsong ea baroreflex, le hypertrichosis. Litlamorao ha li e-so tlaleheloe ha moriana o sebelisetsoa kalafo ea ED, empa liphihlelo li na le meeli.

Molao-motheo oa K+ ho bula seterata hoa khahlisa, 'me liphihlelo tsa pele le minoxidil li bonahala li ts'episa, empa liteko tse laoloang haholoanyane tsa bongaka lia hlokahala ho netefatsa le ho lekola litla-morao tsa lithethefatsi ho bakuli ba nang le ED.

5. α-Adrenoceptor Antagonists.

a. Phentolamine.

Lithuto tsa pele tse nang le phentolamine ea molomo li bontšitse katleho e itseng ho bakuli ba nang le nonspecific erectile insuffence (Gwinup, 1988; Zorgniotti, 1992, 1994; Zorgnotti le Lizza, 1994).Zorgniotti (1992) nkoa e le senokoane, "tlhokahalo" tsamaiso ea phentolamine mokhoa o ts'episang oa kalafo ea ho hloka matla. Becker et al. (1998) o sebelitse teko e laoloang habeli sebakeng se laoloang ke 20, 40, le 60 mg ea phentolamine ea molomo ho bakuli ba nang le ED le monyetla o moholo oa psychanogenic etiology mme a fumana hore moriana o molemong. Ha ho na mathata a tebileng, empa litla-morao tse ling tsa potoloha li ile tsa bonoa kamora 60 mg.

Ho latela lingoliloengHoffman le Lefkowitz, 1996), ts'ebeliso ea phentolamine e kanna ea amahanngoa le kotsi e kholo ea pelo, ho hlahisa khatello ea maikutlo, tachycardia, arrhythmias ea pelo, le liketsahalo tsa pelo tsa ischemic. Leha ho le joalo, liketso tsena li bua ka tšebeliso e matla ea moriana. Oral phentolamine, ka tekanyetso ho fihlela 150 mg, e bonahala e na le litlamorao tse khutšoanyane tsa hemodynamic tsa nako e khuts'oane ho bakuli ba nang le ho nyekeloa ke pelo (Gould le Reddy, 1979; Schreiber et al., 1979). Methapong e hlokahalang bakeng sa ho ntlafatsa likarabo tsa erectile (20-40 mg), ho bile le litlamorao tse fokolang tse mpe tsa pelo (Goldstein, 2000; Goldstein et al., 2001).

Goldstein (2000) 'me Goldstein et al. (2001) e shebile liphihlelo ka phentolamine ea molomo ho ED mme e tlaleha liphetho tsa liteko tse kholo tsa sehlopha sa bolulo sa placebo tse laoloang ke "placebo". Phetoho e bolelang ts'ebetso ea erectile joalo ka ha e hakangoa ke lintlha tsa ts'ebetso ea erectile e ne e phahame haholo kamora ts'ebeliso ea lithethefatsi tse sebetsang (40 mg le 80 mg) ha li bapisoa le placebo. Bakuli ba bangata ba fumanang phentolamine makhetlo a mararo ho isa ho a mane ha ba tlaleha ba khora kapa ba khotsofetse haholo ha ba bapisoa le ba amohelang placebo. Ka tekanyetso ea 40 le 80 mg, ka ho tšoanang, 55 le 59% ea banna ba atlehile ho kenella ka hare ho botšehali ka 51 le 53% e fihlella ho kenella ho 75% ea liteko. Khalemelo ea ED kapa ntlafatso ho karolo e sa tebang ea ho hloka taolo e fumanoe ke 53% ea banna ba nang le lethalamo la 80-mg le 40% ka lethal dose ea 40-mg ea phentolamine. Mekhoa eohle ea karabelo e ne e tšoana ho sa tsotelehe meriana leha e le efe e tšoanang. Ha ho liketsahalo tse bohloko tse mpe. Litlamorao tse atileng haholo tse bonoang e ne e le khatello ea kelello (10%), hlooho ea hlooho (3%), ho tsekela (3%), le tachycardia (3%). Goldstein (2000) 'meGoldstein et al. (2000) etsa qeto ea hore phentolamine e bolokehile, e mamelletse hantle ebile e sebetsa hantle bakeng sa kalafo ea ED. Hore na phentolamine ke phehisano e 'ngoe kapa mefuta e meng ea kalafo ea molomo e lokelang ho bontšoa ho liteko tsa kliniki.

b. Yohimbine.

Yohimbine ke cy e tsebahalang haholo ka lithethefatsi2-AR antagonist e sebelisitsoeng lilemo tse fetang lekholo kalafo ea ED (Morales, 2000b). Setlhare se ikhethile ka mokhoa oa α2-AARI, le haeba liketso tse ling li bontšitsoe (Goldberg le Robertson, 1983), tsena li ka bonts'oa feela maemong a tebileng ao mohlomong a ke keng a fumanoa ho motho. Sebaka sa ts'ebeliso ea yohimbine e le moemeli oa pro-erectile mohlomong ha se potoloho, hobane subtype e ka sehloohong ea li-cy-ARs ka penile erectile tiske ke ea α1-type (Andersson, 1993) le ente ea intracavernosal ea α e 'ngoe e matla haholo2-AR antagonist, idazoxan, ha e hlahise pherekano ea penile ho motho (Brindley, 1986). Ho baithaopi ba phetseng hantle, Danjou et al. (1988) o fumane hore infravenous infusion ea yohimbine ha e na litlamorao tsa erectogenic, e sa khethollang hore yohimbine e tsamaisitsoeng ka molao e kanna ea sebetsa. Halofo ea bophelo ba plasma ea yohimbine e fumanoe e le 0.6 h (Owen et al., 1987), athe litlamorao tsa plasma NA tsa lithethefatsi li bile 12 h (Galitzky et al., 1990). Phapang ena e ka hlalosoa ke ho ba teng ha metabolite e sebetsang (Owen et al., 1987).

Litlamorao tsa yohimbine li fumanoe lipatlisiso litekong tse laoloang ho bakuli ba nang le organic (Morales et al., 1987), psychogenic (Reid et al., 1987), hape le tsoakane (Riley et al., 1989; Susset et al., 1989) etiology ho matla a bona. Ho bakuli ba se nang matla, litlamorao tsa lithethefatsi li bonts'itsoe, ke hore, 43% e arabetse (karabelo e felletseng kapa e fokolang) ho yohimbine le 28% ho placebo (phapang e sa bohlokoa) (Morales et al., 1987). Boithuto ba moralo o ts'oanang, lipalo tse tšoanang li fumanoe ho bakuli ba nang le khatello ea kelello ea kelello, le ha nako ena phapang pakeng tsa kalafo e sebetsang le placebo e ne e le bohlokoa (Morales et al., 1987; Reid et al., 1987). Likarabo tse ntle ho bakuli ba se nang matla a li-etiology tse tsoakiloeng li tlalehiloe hoo e ka bang karolo ea boraro ea linyeoe tsena (Riley et al., 1989; Susset et al., 1989).

Boithuto bo habeli ba bofofu ba crossover habeli ho bakuli ba 62 ba hlokang matla, moo ho sebetsa hantle hoa mafura a yohimbine a sebelisoang sebakeng sa heno botoneng ho bapisoa le a placebo, ho khothalelitse litholoana tse ntle mokhatlong oa bakuli (Turchi et al., 1992), empa ho palo eohle ea batho, ha ho litlamorao tse kholo tse fumanoeng.

Tekanyetso e phahameng ea yohimbine (36 mg ka letsatsi) e fumanoe e se na phello e ntle ho e lebelletsoeng, e sa reroang, e laoloang mahlo a mabeli a sa boneng, thuto ea crossover ea bakuli ba 29 ba nang le mofuta oa ED o kopanengKunelius et al., 1997). Phuputso e 'ngoe e laoloang ke mahlo ea bakuli ba 86 ka bobeli bo hlakileng ntle le lisosa tse bonoang tsa tlhaho kapa tsa kelello (Vogt et al., 1997) e senotse hore yohimbine e sebetsa hantle haholo ho feta placebo (71 bapisoa le 45%) ho latela sekhahla sa karabelo.

Phuputsong e sa sebetseng, e foufetseng habeli, e laoloang ke sebaka, Montorsi et al. (1994) o fumane hore kalafo ea ho kopanya le yohimbine le trazodone e ne e sebetsa hantle ho feta placebo bakeng sa kalafo ea khatello ea kelello ea psychogenic. Boithuto ba Meta bo bontšitse hore yohimbine e phahame ho feta placebo kalafo ea ED (Carey le Johnson, 1996;Ernst le Pittler, 1998).

Jacobsen (1992) e fumane thutong ea sefofane hore bakuli ba robeli ho ba robong ba nang le matla a ho kula a amanang le kalafo ea meriana e thibelang lefu lena le serotonin reuptake blocker, fluoxetine, ba arabile hantle ka yohimbine ea molomo. Ho bonts'oa matla a litlamorao tsa yohimbine ke optiox receptor antagonist naltrexone (Charney le Heninger, 1986).

Litlamorao tse tlalehiloeng tsa yohimbine, ha li sebelisetsoa merero e meng ntle le ea ED, li kenyelletsa keketseho ea sekhahla sa pelo le khatello ea mali, hypotension ea orthostatic, matšoenyeho, ho ruruha le ho fetoha hoa maikutlo (Charney et al., 1982, 1983; Theko et al., 1984). Litla-morao tse bonoang ho bakuli ba nang le ED hangata li bobebe (Morales, 2000b).

Ho ke ke ha qheleloa ka thoko hore yohimbine e sebelisoang ka molomo e ka ba le phello e molemo ho bakuli ba bang ba nang le ED. Liphetho tse hanyetsanang tse fumanehang li ka hlahisoa ke ho fapana ha moralo oa lithethefatsi, khetho ea bakuli, le litlhaloso tsa karabelo e ntle. Leha ho le joalo, ka kakaretso, liphetho tse fumanehang tsa kalafo ha li khahlise (Morales, 2000b).

6. Liphephetso tsa Opioid Receptor.

Ho tlaleha hantle hore ente e sa foleng ea li-opioids e ka lebisa ho theoha ha libido le ho hloka matla (Parr, 1976; Crowley le Simpson, 1978; Mirin et al., 1980; Abs et al., 2000), mohlomong ka lebaka la hypogonadotropic hypogonadism (Mirin et al., 1980; Abs et al., 2000). Ho nahanoa hore li-opioid tsa mehleng ea khale li ka kenella ts'ebetsong ea thobalano, bahanyetsi ba opioid ba khothalelitsoe hore ba atlehe joalo ka kalafo (Fabri et al., 1989; Billington et al., 1990). Likatseng tse sa sebetseng, naloxone e bakile li-erections (Domer et al. (1988), 'me ho fanoa ka tlhahiso ea hore motsoako o ka hlaha ka lebaka la maemo a fetotsoeng a lihormone tse tsoang tsamaisong ea methapo ea kutlo kapa ho tlosoa ha molumo oa kutlo oa mokokotlo ka mokokotlong oa mokokotlo kapa ka boeena ba semola-khang. Ho khahlisang, naloxone e ka hlahisa litlamorao tsa erectile tsa apomorphine ho likhoto (Berendsen le Gower, 1986).

Intravenous naloxone e fumanoe e sena tšusumetso ho ratoang lithutong tse tloaelehileng (Goldstein le Hansteen, 1977). Naltrexone e na le litlamorao tse ts'oanang le tsaxxone, empa e ka fanoa ka molomo mme e na le potency e phahameng le nako e telele ea ts'ebetso (24-72 h) ho feta naloxone. E ananeloa hantle ho tsoa liphatseng tsa ka mpeng empa e tsamaisoa ke metabolism e pharalletseng ea pele, e tšelitsoeng ka har'a sebete 'me e nchafalitsoe ke ho potoloha ha methapo. Metabolite e kholo ea naltrexone, 6-β-naltrexone, le eona e na le ts'ebetso ea antagonist ea opioid mme mohlomong e kenya letsoho litlamorao tsa naltrexone.

Thutong e bulehileng ea sefofane, Goldstein (1986) e fumane hore naltrexone (25-50 mg / day) e khutlisitse ts'ebetso ea erectile ho banna ba tšeletseng ho ba supileng ba nang le "idiopathic" ED. Phuputsong e le 'ngoe e sa boneng letho, Fabri et al. (1989) bapisa naltrexone le placebo ho banna ba 30 ba nang le idiopathic erectile impotence. Ho fumanoe hore ts'ebetso ea thobalano e ntlafalitsoe ho 11 ea bakuli ba tšoaroang ke 15 naltrexone, athe placebo ha e na litlamorao tse kholo; libido ha ea ka ea ameha 'me ho ne ho se na litla-morao. Ka kakaretso, litla-morao tse bohloko tsa naltrexone ha li nke nako ebile li bonolo, empa ho lemala ha hepatocellular ho ka hlahisoa ka litekanyetso tse phahameng.

Phuputsong e hlophisitsoeng e sa laoloang, e laoloang sebakeng, e sa sebetseng habeli ea sefofane sa bakuli ba 20 ba nang le idiopathic, nonvascular, non-neurogenic ED, van Ahlen et al. (1995) ha ea ka ea ba le phello e matla ho libido kapa khafetsa ho tsa thobalano, empa li-erections tsa hoseng haholo li eketsehile haholo.

Keketseho e ntseng e eketseha ea li-peptide tsa opioid e ke ke ea behelloa ka thoko e le sesosa sa ho se atlehe ha erectile mme kalafo ea naltrexone maemong ana e ka ba moemeli ea sebetsang oa kalafo. Leha ho le joalo, lithuto tse laoloang hantle tse netefatsang sena lia haella.

7. Dopamine Receptor Agonists.

Ho thehiloe hantle hore mekhoa ea dopaminergic e ka ba le karolo taolong ea boitšoaro ba banna ba thobalano ho liphoofolo.Bitran le Hull, 1987; Foreman le Hall, 1987). Joalokaha ho hlalositsoe pejana, apomorphine, dopamine receptor agonist e tsosang dopamine D ka bobeli1 le D2 li-receptors, li bonts'itsoe ho kenya letsoho ho kenella ho hoholo litekong (ho likhoto)Mogilnicka le Klimek, 1977; Benassi-Benelli et al., 1979) hammoho le ka tsela e tloaelehileng (Lal et al., 1984) le matla (Lal et al., 1987, 1989) banna. l-Dopa e kanna ea susumetsa tsoekere ho bakuli ba nang le lefu la Parkinson (Vogel le Schiffter, 1983). Ho khothalelitsoe hore dopamine D2 ho hlohlelletsoa ha li-receptor ho ka baka ho kenella ho hoholo litlamong, athe ts'ebetso ea D1 li-receptors li na le litlamorao tse fapaneng (Zarrindast et al., 1992). Ho litšoene tsa rhesus, quinelorane, dopamine D2 receptor agonist, tlhahiso ea penile erection (Pomerantz, 1991), e khahlisa pono eo D2ho hlohlelletsa li-receptor ho bohlokoa bakeng sa karabo ena. Ho ka ba joalo le ka monna (Lal et al., 1989). Leha ho le joalo, liteko tsa tleliniki tse nang le D e khethiloeng2 receptor agonist, quinelorane, e ile ea emisoa pele ho nako pele ts'ebetso ea eona e sebetsang e ka hlahlojoa.

a. Ho kentsoe Apomorphine.

Lal et al. (1984) e bonts'itse thutong e foufetseng e laoloang habeli ea baitlami ho baithaopi ba phetseng hantle hore apomorphine e kentse ka mokhoa o sa sebetseng (0.25-0.75 mg) e ileng ea khona ho susumetsa maikutlo. Sena se tiisitsoe ke Danjou et al. (1988), e bonts'ang hore apomorphine e khelositse mohopolo ebile e matlafalitse mohopolo o susumetsoang ke tšusumetso e mpe ea pono. Ha ho na keketseho ea libido, e neng e lumellana le se hlokometsoeng nakong e fetileng (Julien le Over, 1984). Ho bakuli ba 28 ba nang le bofokoli, Lal et al. (1989) fumane hore 17 e arabile ka erection kamora apomorphine e subcutaneous (0.25-1.0 g); ha ho mohopolo o qalileng ka mor'a placebo. Segraves et al. (1991) e boetse e tsamaisitse apomorphine ka mokhoa o ikhethileng (0.25-1.0 g) ho banna ba 12 ba nang le matla a ho hloka kelello 'meleng thutong e laoloang ke mahlo le ea placebo. Ba fumane keketseho e amanang le lethal dose ea maemo a phahameng haholo a potile. Erection e fetang 1 cm e fumanoe ho 11 ea bakuli ba 12.

Ha ho na ho qheleloa ka thoko hore sehlotšoana sa bakuli ba se nang matla se ka ba le tšenyo ea mesebetsi e bohareng ea dopaminergic le hore molao-motheo oa dopamine receptor stimulation o ka sebelisoa eseng feela ka ho hlahloba empa hape le kalafo. Monyetla oa kalafo oa "subcutaneous apomorphine", leha ho le joalo, o bonahala o fokola haholo ka lebaka la litla-morao tse bang teng khafetsa. Litekanyetso tse phahameng (ke hore, ho fihlela ho 5-6 mg ho bakuli ba baholo) li ka baka khatello ea maikutlo, le lethathamong la litekanyetso tse tlase (0.25-0.75 mg) moo litla-morao tsa penile li ka bonts'ang, emesis, yawning, ho otsela, ho tsitsinyeha hoa pelo, lacrimation, Flush, le ho tsekela (Lal et al., 1984; Segraves et al., 1991) li ka etsahala. Ntle le moo, apomorphine ha e sebetse ka molomo mme e na le nako e khuts'oane ea ketso. Lal et al. (1987) o hlokometse hore lingoli, empa eseng babuelli, li bile le litlamorao tse mpe. Le ha ho le joalo, apomorphine e tsamaisoang ka mokhoa o sa bonahaleng e bonahala e sena sephetho se amohelehang.

b. Oral Apomorphine.

Heaton le basebetsi-mmoho (1995) e tlaleha hore apomorphine, e kenngoeng ka mucosa ea molomo e tla sebetsa e le arhente ea erectogenic. Ho bakuli ba se nang matla ba 12 ba nang le bokhoni bo netefalitsoeng ba erectile empa ba se na sengoloa se ka bonoang, 3 kapa 4 mg ea apomorphine ka foromo e laoloang e laolehileng e hlahisitse li-erections tsa nako e telele ho 67% ntle le litlamorao tse mpe.

Liphetho tsena li netefalitsoe haholo lithutong tse foufetseng tse sa sebetseng tsa mahlo a mabeli (Padma-Nathan et al., 1999; Dula et al., 2000). Thutong eaPadma-Nathan et al. (1999), lipatlisiso tsa 2, 4, 5, le 6 mg li ile tsa hlahlojoa, ka litlamorao tse ntle (litlamorao tse ntle le litlamorao tse nyane) tse fumanoeng ka 4 mg (apomorphine 58.1% bapisoa le placebo 36.6%. Ho hlaha hoa nausea (eseng e matla) ka 4 mg e ne e le 21.4%. Liphetho tse tšoanang li fumanoe lithutong tse peli tse sa sebetseng tsa bofofu tse sa sebetseng ho kenyeletsa bakuli ba 977 ba nang le khatello ea mali (Lewis et al., 1999).

Liphihlelo tse ngata tsa kliniki tse nang le apomorphine 2 e pharaletseng le 3 mg li sa tsoa baka tumello bakeng sa tšebeliso ea bongaka linaheng tse 'maloa. Tlhahisoleseling e fumanehang (Heaton, 2000) e fana ka tlhahiso ea hore subomual apomorphine ke mokhoa o sebetsang hape o sebetsang bakeng sa bakuli ba nang le ED.

8. Trazodone.

Trazodone ke moemeli oa lithibela-mafu "atypical", ea lik'hemik'hale le ea lithethefatsi ka mokhoa o fapaneng le li-antidepressants tse ling tse fumanehang hona joale (Haria et al., 1994). Mokhoa ona oa lithethefatsi o thibela ho kenella bohareng ba 5-HT mme o eketsa phetoho ea dopamine ea boko empa ha e thibele ho khutlisetsoa morao ha NA (Georgotas et al., 1982). Trazodone e boetse e bontšitsoe ho thibela li-receptor tsa 5-HT le dopamine, athe metabolite ea eona e kholo, m-CCP, e na le ts'ebetso ea agonist ho 5-HT2C receptors (Monsma et al., 1993). Mokhoa ona oa metabolite o etsa hore ho be le likhoto 'me ka mokhoa o ikhethileng o eketsa sekhahla sa ho thunya ha methapo ea kutlo (Steers le de Groat, 1989). Mokhoa oa ts'ebetso oa trazodone ka khatello ea maikutlo ha o utloisisehe ka botlalo; e na le ketso e tsebahatsang ya ho susumetsa. Trazodone e na le serum halofo ea bophelo ba hoo e ka bang 6 h mme e na le metabolism e ngata (Haria et al., 1994).

Trazodone le metabolite ea eona e kholo li bonts'itsoe li na le phello ea thibelo ea α-AR liseleng tse arohaneng tsa batho tsa thipa (Blanco le Azadzoi, 1987; Saenz de Tejada et al., 1991b). Krege et al. (2000) e bontsitse trazodone ho ba le tšebeliso e phahameng le e leka-lekaneng ea setho sa motho1- le α2-ARaro, ka ho latellana, le hore setlhare ha se khetholle pakeng tsa subtypes ea α1- le α2-MAROLO. Metabolite e sebetsang, m-CCP, e ne e bonahala e se na litlamorao tse kholo.

Trazodone e laetsoeng ka molomo e amahanngoa le priapism ho banna ba nang le matla (Azadzoi et al., 1990) le ho eketseha ha mantsiboea mosebetsing oa boithaopo ho baithaopi ba phetseng hantle (Saenz de Tejada et al., 1991b). Ha e ente ka mokhoa o kenang hantle ho bakuli ba nang le matla a ho hloka thari, trazodone e ile ea baka ho ruruha empa ha e qalohe ka botlalo (Azadzoi et al., 1990). Intracavernosal trazodone e sebelitse e le mohanyetsi oa α-AR empa e ne e sa sebetse joaloka papaverine kapa motsoako oa papaverine le phentolamine (Azadzoi et al., 1990). Phihlelo e ntle ea kliniki ka moriana o tlalehiloe (Lance et al., 1995). Leha ho le joalo, litekong tse laoloang habeli tsa placebo tse laoloang ho bakuli ba nang le etiology e fapaneng ea ED ea bona, ha ho na tšusumetso ea trazodone (150-200 mg / letsatsi) e ka bontšitsoeng (Meinhardt et al., 1997; Enzlin et al., 2000).

Le haeba tlhahisoleseling e tsoang litekong tsa bongaka tse sa laoloang ka tšohanyetso e sa tšehetse pono ea hore trazodone ke kalafo e sebetsang ho banna ba bangata ba nang le ED, lithethefatsi e ka ba mokhoa o mong ho banna ba bang ba nang le matšoenyeho kapa ba tepeletseng maikutlo.

9. Melanocortin Receptor Agonists.

Melanotan II ke cyclic nonselective melanocortin receptor agonist, 'me e kenngoe butle-butle, ho fumanoe hore e ne e le moqapi oa tšebeliso ea penile erection ho banna ba nang le nonorganic ED (Wessels et al., 1998, 2000). Leha ho le joalo, ho hlohlona / ho otlolla 'me ka linako tse ling ho nyekeloa hoa pelo le ho hlatsa ho fokotsa ts'ebeliso ea eona. Leha ho le joalo, moeli oa "melanocortin receptor agonism" o nang le lithethefatsi tse ikhethileng tsa subtype ke mokhoa o mocha o ka thusang.

V. Liphetho

Karolo ea bohlokoa ea tsamaiso ea methapo e kholo ea methapo ea erectile e ntse e amoheloa. Taolo ea mokokotlo le ea supraspinal ea tšebetso ea erectile e kenyelletsa li-transmitter tse 'maloa, ho kenyelletsa dopamine, serotonin, noradrenaline, nitric oxide, le peptides, tse kang oxetocin le ACTH / α-MSH, empa e ntse e tsebahala ka karolo e itseng. Tsebo e qaqileng ea litsamaiso tsena e tla ba ea bohlokoa ho sibollotsoeng ha li-pharmacological tse sebetsang bakeng sa kalafo ea ED. Le ha lipatlisiso li shebile haholo litseleng tse poteletseng tsa erection mme li lebisitse tlhokomelong ea mantlha ea sebopeho sa ED, mehato e fapaneng e kenyelletsang ho ts'ebetsong ea methapo, ho hasanya maikutlo, le phetisetso e kenang ea lipontšo tsa neural ka mesifa ea penile e hloka lipatlisiso tse ling. Boithuto bo tsoelang pele ba tšebelisano lipakeng tsa li-transmitter / li-modulators tse fapaneng e ka ba motheo oa mekhoa e mecha ea ho kopanya. Ho eketsa tsebo ea liphetoho mabapi le liphetoho tsa penile tisy tse amanang le ED ho ka lebisa kutloisisong e kholo ea methapo ea pathogenetic le ho thibela mafu.

lumela hore baa fokola

Boithuto bona bo tšehelitsoe ke Lekhotla la Patlo ea Bongaka la Sweden (Grant 6837), le Lefapha la Bongaka la Bongaka, Univesithi ea Lund.

Mongolo o botlaaseng ba leqephe

  • 1 Aterese ea mangolo: K.E. Andersson, Lefapha la Clinical Pharmacology, Sepetlele sa Lund University, S-22185 Lund, Sweden. Lengolo-tsoibila: [imeile e sirelelitsoe]

  • Likhaloso:
    ED
    Ho se sebetse ha erectile
    ACTH
    hormone ea adrenocorticotropic
    α-MSH
    cy-melanocyte e hlasimollang hormone
    AR
    adrenoceptor
    cGK
    cyclic GMP e itšetlehileng ka protheine ea protein
    CGRP
    calcitonin liphatsa tse amanang le gene
    Che
    nitric oxide
    NOS
    nitric-oxide synthase
    eNOS
    endothelial NOS
    iNOS
    NOS e sa sebetseng
    NNOS
    neuronal NOS
    ET
    endothelin
    GABA
    γ-aminobutyric acid
    GC
    cyanyasel cyclase
    HO
    heme oxygenase
    5-HT
    5-hydroxytryptamine, serotonin
    IP3
    inositol 1,4,5-trisphosphate
    KATP
    adenosine triphosphate-K e thehiloeng
    KCa
    kh'amera e its'epo ka K calcium
    MLC20
    subinit ea tsamaiso ea lebone la myosin
    MLCK
    myosin lebok le ketane kinase
    MPOA
    sebaka sa medial preoptic
    NA
    norepinephrine
    NANC
    nonadrenergic, noncholinergic
    l-NAME
    NG-nitro-l-arginine methyl ester
    m-CPP
    1- (3-chlorophenyl) -piperazine
    NMDA
    N-methyl-d-motsoana
    PDE
    phosphodiesterase
    PVN
    "nucleus" ea potoloho ea mali
    PG
    prostaglandin
    PHM
    peptide histidine methionine
    sGC
    soluble guanylyl cyclase
    SNO-Glu
    S-nitrosoglutathione
    TFMPP
    N-trifluoromethylphenyl-piperazine
    TX
    thromboxane
    VIP
    vasoactive intestinal polypeptide
    YC-1
    3- (5'-hydroxymethyl-2'-furyl) -1-benzylindazole

 

      

References

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