Ho feto-fetoha ha mokhoa oa Dopaminergic Tsela ea ho Tšoara ho Sebetsang ha Erectile (2016)

2016 Oct; 119 Suppl 3: 63-74. doi: 10.1111 / bcpt.12653.
Simonsen U1, Comerma-Steffensen S2,3, Andersson KE2.

inahaneloang

Mekhoa ea kalafo ea mantlha e khothalletsoang ea mantlha ea erectile dysfunction (ED), phosphodiesterase mofuta oa inhibitors (PDE5i), ka mohlala, sildenafil, e sebetsa hantle ho bakuli ba bangata ba nang le tšimoloho ea methapo, empa phekolo ena ha e na tekano ho banna ba ka bang 5-30%. le ED moo ho nang le lerato la neuronal. Ho na le tlhoko ea mekhoa ea lipale e fumanehang ho phekola maemo. Re hlahloba menyetla ea ho fetola litsela tsa dopaminergic ho ntlafatsa ts'ebetso ea erectile. Dopamine D1 (D1 , D5 ) - le D2 (D2 -D4 ) li-receptor tse joalo sebakeng sa paraventricular, sebaka sa medial pre-optic, lesapo la mokokotlo le lisele tsa erectile li kentse letsoho ho aheng, mme li-agonists tse 'maloa tse etselitsoeng kalafo ea lefu la Parkinson li amahanngoa le libido e eketsehang. Fensetere ea kalafo ea kalafo ea ED e fumanoe ke tsamaiso ea lipuo tse ling tsa kakaretso dopamine receptor agonist apomorphine, empa e ile ea hloleha haholo ka lebaka la ho se sebetse hantle ha ts'ebetso ea erectile ha e bapisoa le PDE5i. Ho qoba litlamorao tse fokotsang litla-morao tse tsamaisitsoeng ke D2 li-receptors, ho nyekeloa le pelo le emesis, dopamine D4 li-receptor agonists li ile tsa qaptjoa, 'me li etsa hore ho ekehe litoeba, empa meriana ena ha ea ka ea hlahisoa ka kotloloho. Β-lactamase inhibitor clavulanic acid e eketseha dopamine le serotonin mme ea fumanoa e eketseha thobalano tsosa le lits'oants'o, empa khefutso ea karabelo e bell-e bopehile. Bupropion e na le khetho ea ho thibela dopamine pheta seporo hape e ka sebelisoa ho fokotsa thobalano matšoao a bakoang ke meriana e meng e loantšang khatello ea maikutlo, ke ka hona a fanang ka mokhoa o khahlisang oa ho phekola ED. Ka kakaretso, modulation ea dopaminergic pathways e fana ka monyetla oa ho ntlafatsa kalafo ea ED.

PMID: 27541930
DOI: 10.1111 / bcpt.12653

Moetso ke ketsahalo ea hemodynamic moo vasodilatation ea intracavernous intracavernous le helicine methapo e lateloang ke ho eketseha ha mali a tsoang metsing ho ea k'holeseteroleng ea k'holera. Ho qaptjoa ho kenyelletsa mekhoa e fapaneng e bohareng le e poteletseng ea neural le / kapa ea humoral 1. Li-neurotransmitters le li-neuropeptides li ka tsamaisa, ho etsa mohlala, dopamine (DA), kapa inhibit (mohlala, li-peptides tsa opioid) ka ho sebetsa libakeng tse 'maloa tsa boko. Serotonin e ka fana ka litlamorao tsa ho tsamaisa le tse thibelang, ho ipapisitse le subtype e amehang 2.

Li-neurotransmitters tsa Peripheral tse lokollotsoeng ho kutloelo-bohloko (noradrenaline, ATP) le parasympathetic (acetylcholine, nitric oxide, vasoactive intestinal peptide) methapo e kenang ka har'a coora cavernosa, Corpus spongiosum le glans penis e laola phallo ea mali nakong ea kemelo le detumescence 1, 3, 4. Ho metabolic syndrome le lefu la tsoekere, neuropathy hammoho le ho se lekane pakeng tsa lithibelo tsa pelehi tsa phomolo le boikhathollo lithetleng tsa erectile li ka kenya letsoho ho se sebetseng ha erectile dysfunction (ED) 5.

Litataiso tsa hona joale li khothaletsa mofuta oa phosphodiesterase mofuta oa inhibitors 5 (PDE5i), sildenafil, vardenafil, tadalafil le avanafil, e le kalafo ea pele ea ‐ ea ED; leha ho le joalo, banna ba ka bang 30-40% ba nang le ED ha ba arabele kalafo ea inhibitor ea PDE5 6, 7. Bakuli ba nang le tšenyo ea methapo, lefu la tsoekere kapa lefu le matla la methapo ba kanna ba haneloa ke li-inhibitors tsa PDE5 8. Ntle le maloetse ana, meriana ea mathata a methapo ea methapo (CNS), joalo ka li-antidepressants, antipsychotic le anxiolytics, le tsona li na le tšusumetso e mpe mosebetsing oa erectile 5. Li-antidepressants, joalo ka ho khetha li-serotonin reuptake inhibitors (SSRIs) le venlafaxine, li ka ama hampe ts'ebetso ea thobalano ea monna (takatso / ho tsosa-thabo). Li-antidepressants tse ling, joalo ka bupropion, nefazodone le mirtazapine, le tsona li ama ts'ebetso ea thobalano, leha maemo a ts'ebetso ea thobalano a le tlase, ha a bapisoa le SSRI 9. Ntle le mathata a maikutlo, li-antidepressants li boetse li sebelisetsoa ho phekola bohloko ba neuropathic; ka hona, ho se sebetse hantle ka thobalano ho susumetsoang ke li-antidepressants ho ama bongata. Litekong tse ling tsa kliniki, sildenafil e ile ea lokisa ED e hlahisoang ke meriana ea antidepressant; leha ho le joalo, ka lebaka la palo e ntseng e eketseha ea batho ba sa arabeleng ho li-inhibitors tsa PDE5, ho na le tlhoko ea mekhoa ea lipale tse fumanehang kalafo ea ED. Mokhoa o kanna oa se ke oa shebisa feela litsela tse potileng empa o tla boela a tsepamise litsela tse bohlokoa bakeng sa ts'ebetso ea erectile. Joalokaha ho se ho boletsoe, letoto la li-neurotransmitters le kentse letsoho ts'ebetsong ea erectile maemong a mahareng le a potelletseng le letoto la litlhahlobo tsa morao-rao li shebile molao ona ka botlalo 1, 2 le lithuto tsa tliliniki tse amanang le ho se sebetse hantle ka thobalano le monoamine 10. Tlhahlobo e akaretsang e akaretsang tse ling tsa lithethefatsi tsa morao-rao tse tlasa nts'etsopele ea ED le eona e ka khothaletsoa 11. Bakeng sa kalafo ea lefu la Parkinson, litlhare tse 'maloa tse nang le phello ea dopaminergic li ile tsa ntlafatsoa,' me e 'ngoe ea lithethefatsi tsena ka kakaretso dopamine receptor agonist, apomorphine, e fumanoe e hlohlelletsa tsoho 12-15. Ka hona, sepheo sa MiniReview ea hona joale ke ho nahana ka monyetla oa ho fetola litsela tsa dopaminergic ho ntlafatsa ts'ebetso ea erectile.

Dopaminergic Pathways E Akaretsang Mosebetsing oa Erectile

Litsela tse bohareng

Litsela tse bohareng tse kenyang taolo ea ts'ebetso ea erectile li kenyelletsa libaka tse 'maloa tsa boko ba kelello joalo ka sebaka sa medial pre ‐ optic (MPOA), sebaka sa patellricular nucleus (PVN) sa hypothalamus, sebaka sa likarolo tse ka hare tsa mokokotlo, hippocampus, amygdala, khubu ea boroko le stria terminalis, bokellane ba methapo, medulla oblongata le thapo ea lesapo la mokokotlo 2, moo PVN ea hypothalamus le sebaka sa tšohanyetso li leng bohlokoa haholo 2, 15. Letoto la li-neurotransmitters li ameha ho taolo e bohareng ea erection mme li tsamaisa tšebetso ea erectile (dopamine, nitric oxide, glutamate, acetylcholine, oxetocin, hexarelin peptide, ACTH, MSH le pro ‐ VGF), inhibit erectile mosebetsi (mohlala, noradrenaline, enkephalins GABA le endocannabinoids) kapa maemong a serotonin ka bobeli a thusa le ho thibela ts'ebetso ea erectile 2. Dopamine ke neurotransmitter e ka sehloohong ho CNS mme e thusa ho susumetsa takatso ea thobalano, ho qopitsa le maikutlo a botona kapa botšehali 1, 16. Dopamine, eo ho nahanoang hore ke ea bohlokoa bakeng sa ts'ebetso ea erectile, e fumaneha ho MPOA le PVN ea hypothalamus le li-nucleus accumbens. Libaka tsena tse tharo li fumana bolulo ba dopaminergic ho tsoa tsamaisong ea incertohypothalamic 17. Ho PVN, dopamine e lebisa ts'ebetsong ea li-neurone tsa oxytocinergic mohlomong ka ho eketseha ha calcium ea intracellular e lateloang ke ts'ebetso ea neuronal nitric oxide synthase (nNOS). Nitric oxide ka cyclic GMP ‐ tsela e ikemetseng mohlomong nitrosylation e nahanoa e lebisa ts'ebetsong ea li-neurons tsa oxytocinergic (feiga. 1). Nitric oxide e thehoa ke NNOS le castration hape le exo native testosterone, ka ho latellana, tlase ‐ le h ‐ laola polelo ea li-nNOS ho PVN 2.

setšoantšo

Setšoantšo sa 1

Bula sebali sa lipaloPowerPoint
Litsela tsa dopaminergic tse kenyelletsoang ho penile erection (e huleloang ka bosoeu). Ho nahanisisa, ho hopola lintho, ho susumetsa, ho bonts'a maikutlo le ho ba le tšusumetso e ntlafalitsoeng ka cortex 'me ho lebisa maemong a eketsehang a dopamine ka har'a patellarular nucleus ea hypothalamus e lateloang ke ts'ebetso ea dopamine D2, D3, D4 li-receptors le keketseho ea tšebetso ea methapo ea methapo ea methapo ea methapo ea methapo ea methapo ea methapo ea kutlo. Ho kenngoa tšebetsong ha dopamine receptor karolong ea lumbosacral ea lesapo la lesapo la mokokotlo le ka har'a lithane tsa erectile le hona ho kentse letsoho ho bokeng.

Ntle le moo, ho fumanoe li-neuron tsa dopaminergic tse tsamaeang ho tloha ho caudal hypothalamus ho kenella kahare ho mothapo oa moea o ikemetseng le somatic nuclei lumbosacral spinal 18, 19. Ka hona, dopamine e ka lebelloa ho nka karolo taolong ea likarolo le litekanyetso tsa boits'oaro le tse ling tsa penile reflexes.

Morero oa "neurons" oa "PVN oxytocinergic neurons" ho ea ho neurohypophysis le likarolo tse ling tsa boko, empa hape le medulla oblongata le lesapo la mokokotlo, moo ho lebisang ts'ebetsong ea pro ‐ erectile lumbo ‐HTML ea parasympathetic neurons e ka hare ea genitalia.

Litsela tsa spinal

Kamoo ho bonahalang kateng, tsela ea lesapo la mokokotlo e boetse e bohlokoa bakeng sa tšebetso ea erectile. Li-fibers tse sa sebetseng ho dopamine li teng ka har'a ketane ea kutloelo-bohloko ea thoracolumbar hape le mokokotlong oa lumbosacral parasympathetic nucleus 20, 21. Ho feta moo, dopamine e matla ea D2 polelo ea receptor e fumanoe ho lumbosacral parasympathetic neurons 22. Ts'ehetso e ngoe bakeng sa tsela ea dopaminergic maemong a lesapo la mokokotlo e tsoa liphatlalatsong tsa hore likhoto tse nang le maqeba a lesapo la mokokotlo karolong ea thoracic T8, dopaminergic agonist apomorphine e kenelletseng ka mokhoa o hlophisehileng e khona ho susumetsa litšitiso ho likhoto ka mochine o kopantsoeng ke dopamine D2 recagor antagonist (haloperidol, sulpiride) mme e tsamaisoa ke dopamine D1 Mohanyetsi oa receptor (SCH23390) 23. Maikutlo ana a boetse a tšehelitsoe ke ho bona hore taolo e etsoang ka botebo ea apomorphine e etsa hore likarabo tsa boithati tsa erectile li se ke tsa hlaha. 24.

Litsela tsa paripheral

Peile erection e qalisoa ke ho thibela methapo ea kutloelo-bohloko le ts'ebetso ea methapo ea kutlo ea "parasympathetic pelvic" e lebisang ho phumaneng ha methapo ea kutlo le boikhathollo ba lisele tsa mesifa tse boreleli tsa erectile. Sena se lumella ho tlatsoa hoa mali ka litlolo tse tsoang ka bongata le ho thibeloa ha phallo ea mali, le ho kenngoa ha mali a hateletsoeng ka har'a k'holeseterole e kopaneng. Ho lokolloa ha nitric oxide ho methapo ea kutlo ea parasympathetic ho bapala karolo ea bohlokoa bakeng sa boikhathollo, mme keketseho ea mali e kenang ho botoneng nakong ea kemaro e boetse e tsosa sekhahla sa endothelial sa cell ho lokolla nitric oxide le li-vasodilators tse ling tse its'etelletsang ho boloka maqhubu. 25-27.

Ho fapana le karolo ea dopamine ho CNS, karolo ea dopamine ho lithane tsa pherekano erectile ha e hlake hantle. Ts'oaetso ea dopamine induces erection likatse 28, le mohanyetsi oa dopamine D1 li-receptors, SCH23390, ka mokhoa o hlakileng li thibela ho eketseha ha khatello ea intracavernosal e hlahisoang ke ho tsosa methapo ea kutlo ka har'a litoeba 29. Dopamine D1 le D2 li-receptors li hlahisoa ka lithane tsa erectile ho tsoa ho likhoto le monna 30, 31, le patch clamp ea lisele tse boreleli tsa mesifa e tsoang ho Corpus cavernosum e bontšitse hore dopamine le dopaminergic agonists li khatholla ka ho bula lits'ebeletso tse kholo tsa "calcium" ‐ activated potasiamo 32. Ho na le bopaki ba polelo ea "transporter" ea dopamine liseleng tsa endothelial tsa methapo ea methapo 33, 34, empa sena ha se e-so hlahlojoe liseleng tsa endothelial tsa tishu ea erectile. Leha dopamine e ka thehoa litsing tsa kutlo tsa kutlo ea kutloelo-bohloko, mohloli oa dopamine liseleng tsa erectile o ntse o ka hlakisoa, le hore na dopamine e amehang ho erection e tsoa ho endothelium kapa likarolo tse ling ka har'a lithane tsa erectile.

Ka kakaretso, dopaminergic pathways e CNS le karolong ea lumbosacral ea lesapo la mokokotlo e kentse letsoho mesebetsing ea erectile, mme ho tishu ea erectile mohlomong ho na le tsela ea dopaminergic. Sena se fana ka maikutlo a hore ho feto-fetoha ha methapo ea dopaminergic ho ka lebisa maemong ohle a mararo kapa lithethefatsi tsa hydrophilic tse shebileng feela litsela tse kopaneng tsa dopaminergic.

Pharmacological Modulation ea Dopaminergic Pathways ea ho Ntlafatsa Ts'ebetso ea Erectile

Dopamine receptor agonists

Lithethefatsi tsa pele tse nang le tšusumetso ea dopaminergic tse fumanoeng ho etsa hore motho a ikopanye, e ne e le "dopaminergic receptor agonist" e akaretsang 12, mme boholo ba bopaki bo amanang le litlamorao tsa pro ‐ erectile bo fumanoe bakeng sa dopaminergic receptor agonists. Ho na le li-subtypes tse hlano tsa sehlooho tsa dopamine receptors D1-D5 sehlopha sa D1‐ Like (D1, D5), le D2‐ Like (D2, D3 le D4) li-receptors. Li-affinities tse kopanyang li hlalosoa bakeng sa li-dopamine receptor agonists tse tafoleng 1, leha seo ha se hlile se tsamaisana le litlamorao tse sebetsang tsa lithethefatsi ho li-receptor tse amehang. Tse ling tsa lithethefatsi ke li-agonists tse ling ho li-receptor tse bolelang hore ho tsepamisa mohopolo ho hoholo ho ka sitisa endo native ligand dopamine. Ho feta moo, ho hlalositsoe homo‐ le li-heterodimers tsa li-receptor tsa dopamine, 'me seo se ka boela sa fetola tumellano le phello ea bo-ramahlale ba loketseng 35.

Tafole 1. Affinity ((log Ki) ea dopamine receptor agonists bakeng sa dopamine D1-5 Li-receptors
D1 GαS cAMP ↑, Ca2+↑D2 Gi/Go CAMP ↓, K+↑D3 Gi/Go CAMP ↓, K+↑D4 Gi/Go CAMP ↓, K+↑D5 GαS cAMP ↑
Dopamine4.3-5.24.7-7.26.4-7.37.66.6
Apomorphine5.3-6.27.6 (PA)6.1-7.68.4 (PA)6.4-7.8 (PA)
Bromocriptine6.2 (PA)7.37.1 (PA)-6.3 (PA)
Fenoldopam6.5-7.9--6.5-
Cabergoline6.79.0-9.2 (PA)9.17.3 (PA)7.7
Khauta5.9-6.57.5-7.68.37.26.0-7.5
Ropinirole-8.17.7--
Rotigotine5.610.28.47.36.0
Lisuride7.29.2-9.59.3 (PA)8.3-
Quinpirole-4.9-7.76.4-8.07.5-
Quinelorane-5.5-5.77.2-7.4--
PD168,077---8.8 (PA)-
EA-724-<5-7.2 (PA)-
EA-670-<5-5.8 (PA)-
  • Tafole e se e hahiloe ho latela leseli la tlamahanyo ea li-dopamine receptors tse fumanehang database: www.guidetopharmacology.org ke ea International Union of Pharmacology (IUPHAR) le Mokhatlo oa Brithani oa Bongaka oa Borithane, moo litšupiso li fanang ka litekanyetso tsa pele le tsona li ka fihlelisoang. Ha mefuta e fanoa, e bonts'a tlamo ea subppe ea subeptpe. Mabapi le ABT 724, the Ki boleng bo tsoa mosebetsing oa pele 57. Ba bang ba agonists ba tšoauoa ka ho ba karolo e itseng ea agonists (PA) ho li-receptor. Liprotheine tsa G le li-transduction pathways li koahela feela litsela tsa khale. Bakeng sa litlhaloso tse qaqileng, ka kopo bona mongolo 35.

Li-receptor tsa Dopamine li nkoa li tšoaea litselana tsa "protein" tsa "protein", moo D1Li-receptors tse kang ((D1 le D5) banyalani ba GíS protheine le ts'ebetsong e susumetsa li-cyclase tsa adenylate le ho eketsa cyclic AMP, ha D2Li-receptors tse kang ((D2, D3 le D4) banyalani ba Gíi/ Gcy0 protheine le inhibit adenylate cyclase e lebisang ho litekanyetso tse fokotsang tsa cyclic AMP 35, 36. Leha ho le joalo, haufinyane tjena, dopamine D1Li-receptors tse kang "also" li boetse li fumanoe li ts'oarella ho eketsa khalsiamo e tsoelang pele mohlomong ka Gαq e lateloang ke ts'ebetso ea phospholipase C le tokollo ea calcium ea intracellular ka inositol triphosphate (IP3) 35, mme seo se ka 'na sa hlalosa dopamine D1 receptor ‐ e bakang keketseho ea khalsiamo le nitric oxide sebopeho (feiga. 1). Le D2Li-receptors tse kang "li-receptors le" kapa li-heterodimers tsa dopamine receptors li hlalositsoe li nyalana le mekhoa e meng ea phetisetso ea matšoao ka bobeli ka Gβγ le bindin 35. Ka hona, ka lebaka la khethollo e mpe ea ba bang ba agonists, litlamorao tsa tšebetso ea agonists tse amanang le tumellano e tšoanang li ka fapana haholo.

Apomorphine

Ho na le lingoliloeng tse ngata tse buang ka apomorphine le tšebetso ea thobalano 1, 37. Ka bokhutšoanyane, apomorphine ke agonist e akaretsang ea dopamine e amanang le tumellano ea "receptor" e tlamang.Ki) bakeng sa li-receptor tsa dopamine ka tsela e latelang: D1‐ Like [D1 (101 nM), D5 (10 nM)] le D2‐ Like [D2 (32 nM), D3 (26 nM), le D4 (2.6 nM)] 38 (tafole 1). Ho "supraoptic nucleus" (SON), MPOA, le PVN ea hypothalamus, li-neurons tsa oxytocinergic li hlahisa D2, D3 le D4 li-receptors, le apomorphine e ile ea khothaletsoa ho susumetsa mohopolo ka ts'ebetso ea D2Li-receptors tse kang "PVN" 39. Ts'ebetso ea mokokotlo oa dopamine D2 li-receptors le tsona li ka bapala karolo ea phello ea pro ‐ erectile ea apomorphine joalokaha ho boletsoe kaholimo 23. Matsumoto et al. 40 o fumane hore ho ratoa erectile tishu apomorphine ‐ boikhathollo bo khathollang ho bonahala bo kenyeletsa dopamine D1 le D2 li-receptors, empa bangoli ba phethile ka hore "maemong a loketseng a apomorphine, litlamorao tsa potoloho ha li na monyetla oa ho kenya letsoho ho litlamorao tsa projeke ho litoeba '. Ka hona, boemo bo kopanyang le lithuto tsa tšebetso ea erectile li na le karolo e kholo ea karolo ea D2Li-receptors tse joalo ka the erectile phello ea apomorphine.

Apomorphine e entsoe bakeng sa kalafo ea lefu la Parkinson, empa tšitiso e kholo ke ho qhekelloa le ho hlatsa. Leha ho le joalo, ka tsamaiso ea lipuo tse 'maloa tsa apomorphine, fensetere e mamellehang ea kalafo e fumanoe e lumella ho kenella le ho theola sekhahla sa litla-morao (ho tsokotsa, ho nyekeloa ke pelo, ho hlatsa, ho tsekela, pono e lerootho, diaphoresis, pallor, hypotension le bradycardia) e hlokometsoeng ke intranasal tsamaiso ea apomorphine 41. Thutong ea karolo ea III ea phello ea apomorphine ho ED e nang le ho se sebetse hantle ho isa ho - ho matla ho 74% ea banna, li-erections tse bakiloeng ke apomorphine li etsahetse 10-25 min. kamora tsamaiso. Ho feta moo, apomorphine thutong ena e lebisitse ho erection e loketseng thobalano ho 54.4% khahlano 33.8% sehlopheng sa placebo 42. Leha ho le joalo, thutong ea morao-rao ea ho bapatsa ka hloko ea cohort ho banna ba 11,185 ba hlahang le ED ka ts'ebetsong e akaretsang, lebaka le ka sehloohong la ho emisa kalafo ka apomorphine ke hore lithethefatsi li ne li sa sebetse ho 64.7% ea bakuli 43.

Joalokaha ho se ho boletsoe, apomorphine e na le letoto la litlamorao tse ka ba mpe. Litlamorao tse atisang ho hlaha ha apomorphine thutong ea papatso ea post ‐ e ne e le hlooho 43, joalo ka hypotension le yawning, phello ena e kanna ea boleloa ke phello ea li-receptor tsa dopamine. Leha ho le joalo, apomorphine e boetse e bonts'itsoe maemong a tlase a ho kenya tšebetsong menyetla ea nakoana ea li-receptor ankeptin 1 (TRPA1) tse kenyelletsang maikutlo a bohloko, ho ruruha le ho nyekeloa hoa pelo 44, e fana ka maikutlo a hore ho tlama sepheo ho tlatsetsa ho litlamorao tsa apomorphine.

Dopamine e khethiloeng1 li-agonists tsa receptor le tšebetso ea erectile

Lithutong tsa pele tsa phello ea apomorphine microinjected ho PVN, phello ea pro ‐ erectile e koetsoe ka bobeli ke dopamine D1 recagor antagonist, SCH 23390, le dopamine D2 antagonists ea li-receptor, haloperidol le (-) - sulpiride 12. Fenoldopam ke benzazepine e tsoang le agonist e ikhethileng ea ho khetha ka ho khetheha ho dopamine D1 li-receptors (tafole 1) hape ha e na kamano ea bohlokoa bakeng sa dopamine D2 li-receptors, empa li tlama le botsitso bo leka-lekaneng ho α2‐Adrenoceptors. E ngolisitsoe e le sethethefatsi sa antihypertensive haholo-holo bakeng sa ho phekola koluoa ​​ea khatello ea mali le / kapa lefu la methapo ea methapo. Ts'ebetso ea ts'ebetso ea lethal dose ea fenoldopam ‐ e ts'episitse keketseho ea khatello ea methapo (tekanyo ea ts'ebetso ea erectile) e susumetsoang ke ts'usumetso ea motlakase ea karolo e tlase ea mokokotlo oa methapo ea methapo ka har'a litoeba tse amoheloang. 45. Le hoja in vitro lithuto li bonts'itse karolo ea nitric oxide boitapisong ba corpus cavernosum e hlahisitsoeng ke fenoldopam le dopamine e 'ngoe1 li-agonist tse khethang li-receptor, A ‐ 68930 31, 45, ka vivo phello ea pro ‐ erectile ea fenoldopam e phehelletse boteng ba inhibitor ea NOS e fana ka maikutlo a hore ho na le phello e tobileng ea proenretile ea fenoldopam. Leha ho le joalo, liphumano tsena li hloka ho netefatsoa ke lithuto tse ling, hape e tla ba ho khahlisang ho hlakisa hore na taolo ea lehae kapa tsamaiso ea methapo ea fenoldopam liphoofolong tse sa tsebeng letho le / kapa motho o lebisa sehlohlolong.

Dopamine e khethiloeng2 le D3 li-agonists tsa receptor le tšebetso ea erectile

Ho tšoana le apomorphine, dopamine D2/D3 agonists, bromocriptine le quinelorane, li etsa meketjana ea boithatelo le ho eketsa palo ea liketsahalo tsa erectile ka likhoto 46-48, mohlomong ka ts'ebetso ea li-neuron tsa oxytocinergic ho PVN ea likhoto 47. Dopamine D2 le D3 li-receptor li na le 50% homology ka sebopeho, mme ho bonahetse ho le thata ho fumana likhomphutha tse khethiloeng bakeng sa dopamine D3, joalo ka D2, li-receptors 49. Dopamine D2 li-receptors e bile sepheo sa kalafo ea mathata a motsamao a amanang le lefu la Parkinson le dopamine D.2 agonists, ha modulation ea dopamine D3 li-receptor li bohlokoa bakeng sa kalafo ea lefu la Parkinson, ho lemalla lithethefatsi le schizophrenia 49, 50. Li-agonists tse 'maloa tsa dopamine, mohlala, bromocriptine, cabergoline, perarama, ropinirole le rotigotine, tse sebelisetsoang kalafo ea lefu lena li na le dopamine D2 receptor agonist litlamorao (tafoleng 1), Hape li ka amahanngoa le ho eketseha ha libido (bosodoma). Erection e telele (> 4 hr) e hlalosoang e le bohlokoa ho motho e hlalositsoe haeba ho ka ba le litlaleho tsa cabergoline le rotigotine 51, 52 hape e senya ts'ebetso ea erectile. Ntle le phello ho dopamine D2 li-receptors, cabergoline le rotigotine ka bobeli li tlama le ho hanyetsa α1‐Adrenoceptors, le antagonism ea α1‐Adrenoceptors ke sesosa sa khaolo ea kemelo 53.

Palo ea lithuto tse hlahlobang phello ea dopamine D2 le D3 agonists bakeng sa kalafo ea ho se sebetse ka thobalano e na le moeli. Tekong e le 'ngoe e bulehileng moo bakuli ba 13 ba tlalehileng ho se sebetse ka thobalano kamora hore ba qale ka kalafo ea ho imeloa kelellong, ts'ebetso ea thobalano, e lekantsoeng ka ts'ebeliso ea sekala sa Arizona Sexual Experience Scale le Clinical Global Impression of Improvement scales, e bonts'itseng phello e kholo likekeleng ka bobeli libeke tse 3 kamora ho qala kalafo. le ropinirole 54. Tekanyo ea ropinirole (3-4 mg / letsatsi) thutong ea morao-rao e ne e le tlase haholo ho feta tekanyetso (20-25 mg / letsatsi) e hlalositsoeng e baka bosodoma le litakatso tsa thobalano ho bakuli ba nang le lefu la Parkinson. 10, 54. Ka hona, menyetla ea ho phekola ED ea tlhaho e tsoakiloeng ke li-agonists tse ikhethileng tsa dopamine D2 kapa D3 li-receptor li ntse li lokela ho hlahlojoa, leha ho le joalo, litlamorao ho litlamorao tse mpe tse kang boits'oaro le khatello ea mali li lokela ho tsotelloa. Ntle le moo, ho ka ba molemo ho etsa lithuto tse sa sebetseng tse sa sebetseng tse sebelisang mahlo a marang-rang bakeng sa ho phekola khatello ea maikutlo.

Dopamine e khethiloeng4 li-agonists tsa receptor le tšebetso ea erectile

Dopamine e ikhethileng ea D4 receptor agonist, PD168077, e fumanoe e ts'oarana le litheko ho likhoto ha li-kenya letsoho ka har'a PVN 47, 55, 56. Leha ho le joalo, ka ho ts'oarela Fos ho li-oxytocinergic neurons ho PVN, PD168077, ho fapana le quinelorane, ha hoa ka ha fumaneha ho kenya tšebetsong li-neuron tsena. Ho feta moo, phello ea PD168077 e ne e itšetleha ka maemo; mohlala, litlamorao li ile tsa bonoa boteng ba likhoto tsa basali tse amohelang mme li ka kenyelletsa dopamine D4 ts'ebetso ea receptor ea tsamaiso ea "magnocellular oxytocin" 47.

Apomorphine e na le tšebelisano e phahameng ea dopamine D4 li-receptors, empa hape e tlama ho dopamine D2 li-receptors tse nang le kamano e phahameng (tafole 1). Ho qoba litekanyetso tsa litekanyetso tse fokolisang litla-morao2 receptors, ho etsa mohlala, ho nyekeloa le pelo le emesis, dopamine D4 li-agonists tsa li-receptor, ABT 724 le ABT 670, li ile tsa ntlafatsoa bakeng sa kalafo ea ED. Ka litoeba tse tsamaeang ka bolokolohi, keketseho ea khatello ea intracavernosal e lekantsoe mme ea bonts'a hore ABT 724 e sebelisoe ka mokhoa o ikhethileng ‐ ka tsela e ikhethileng e eketse maemo le bophahamo ba li-erections tsa boithatelo, 'me likarabo tsena li ne li le kholo ebile e le tsa nako e telele boteng ba PDE5i, sildenafil 57. Ho kenella lipapatsong tse tebileng, joalo ka mohlala oa pele ho nausea le emesis, ho senotse hore ho fapana le dopamine e khethiloeng2 receptor agonist, PNU ‐ 95666E, ABT 724 ho ena le litekanyetso tse phahameng ha li na litlamorao tsena 57. Dopamine e 'ngoe hape4 receptor agonist, ABT 670, e nang le bioavailability e tsoetseng pele ea molomo e hlahisitsoe, empa e bontšitse hore e amana haufi le dopamine D4 li-receptors ha li bapisoa le ABT 724 (tafole 1, 58). E laoloe ka tsela e sa sebetseng, maemo a ABT 670 ‐ erections tsa penile a ne a sa fuoe hloko ka tekanyo e le 'ngoe ea apomorphine 58. Lintlha tsena li lumellana le tlhokomeliso ea hore ABT 724 le ABT 670 ha e na matla ebile ha e sebetse hantle ha e bapisoa le apomorphine, mohlomong le eona e hlalositsoe ke tlhokomeliso ea hore ke karolo e sa sebetseng hantle ea bongaka ho dopamine D4 Li-receptors 57, 58. Ntshetsopele ea dopamine D tsena4 li-agonists, ABT 724 le ABT 670, li fihlile, ka ho latellana, liteko tsa methati ea I le ea II. Ka hona, leha ho bile le litlamorao tse fokolang tse hlakileng le ABT 724 le ABT 670 ha li bapisoa le apomorphine, potency le katleho e ne e le tlase. Mona, hape ho fumaneha hore phello ea erectile ts'ebetso ea dopamine D4 li-receptors ho itšetleha ka moelelo li ka bapala karolo ea sephetho.

Dopamine e khethiloeng5 li-agonists tsa receptor le tšebetso ea erectile

Tlhahisoleseling mabapi le phello ea dopamine D5 receptor agonists mabapi le ts'ebetso ea thobalano e na le moeli. Ho entsoe liphuputso tse 'maloa ho supa likarolo tsa polelo ea dopamine D5 li-receptors. Dopamine D5 receptor e hlahisoa ho hypothalamus le "parafascicular" nucleus bokong ba rat le motho. Libaka tse fapaneng tsa polelo bakeng sa dopamine D5 Li-receptors khahlano li-receptor tse ling tsa dopamine li fana ka maikutlo a hore dopamine D5 li-receptors li bapala karolo ea bohlophisi le motsoako oa tšebetso ea dopaminergic 59. Dopamine D5 li-receptors li boetse li hlahisoa libakeng tse ling tsa boko, ka mohlala, substantia nigra ‐ pars compacta, striatum, cortex ea "cerebral" cortex, nucleus accumbens le tubercle ea olgicory 60. Tlaleho ea morao-rao e bontšitse hore ho kokota ha dopamine D5 li-receptors li fokotsa ho ratoa ha thobalano litsoeng tsa basali le ho banna tse susumetsang litlamorao tse tlisoang ke ho kenella pele ho kenella 61. Phokotso lithahasellong tsa botona le botšehali, mathata a ED le ejaculatory a teng ho bakuli ba nang le li-antipsychotic 62. Ka hona, dopamine D5 receptor agonist e ka ba tlatsetso ea ho ntlafatsa maikutlo a thobalano mme mohlomong le libido ho bakuli bana.

Ka kakaretso, ho hlohlelletsa agonist ea li-receptor tsa dopamine ke tsela e tsoetseng pele ea ho fumana litlamorao tsa pro-rectile, 'me li-receptors tsa dopamine tse bohareng le tse haufi ke liphofu tse ka bang teng bakeng sa kalafo ea ED. Ho bonahala eka litlamorao tsa erectile li its'etleha ts'ebetsong ea dopamine D2, D3, D4 li-receptors ho CNS le ho potoloha ho latela haholo ho itšetleha ka dopamine D1 ts'ebetso ea receptor ho corpus cavernosum (feiga. 1). Le ha apomorphine e hlahile e le sethethefatsi se ts'episang bakeng sa kalafo ea ED, e emetse moloko oa pele. Tlhokahalo ea moloko o latelang e tla ba hore ba khethang lithethefatsi ba na le bonyane katleho e tšoanang ho, mohlala, D3/D4 li-receptors 'me ka nako e ts'oanang qoba litlamorao tsa apomorphine.

Dopamine receptor antagonists le tšebetso ea erectile

Li-antipsychotic le tšebetso ea erectile

Boholo ba lithethefatsi tsa antipsychotic bo tlama le ho hanyetsa phello ea dopamine ho dopamine D2 li-receptors, ka mohlala haloperidol. Ka hona, lithethefatsi tsa kalafo ea anti-anti psychotic hangata li amahanngoa le ho fokotseha ha mmele ho bakuli ba 30-60%, ha lingaka tse ncha tsa anti ‐ ho bonahala li na le tlokotsi e tlase ea ho se sebetse ka thobalano. 5, 62. Har'a li-psychotic tse ncha tsa anti ‐ psychoses, risperidone e bonahala e na le tekanyo e phahameng ka ho fetisisa ea khatello ea thobalano, ha ho ntse ho na le data e sa lekaneng ho aripiprazole le ziprasidone. Phuputso e entsoeng ka sefofane e fetolang kalafo ho tsoa ho li-antipsychotic tsa atypical, risperidone, amisulpride le olanzapine ho aripiprazole ho bonahala e ntlafalitse ts'ebetso ea thobalano ho palo e fokolang ea bakuli 63, empa sena se hloka ho netefatsoa ke lithuto tse nang le palo e kholo ea bakuli.

Ho thata ho arohanya maloetse le phello ea lithethefatsi le ho fumana leseli le tšepahalang ho bakuli ba nang le lefu la psychotic. Kahoo, ho hloka ts'ebetso ea thobalano e amanang le kalafo ea antipsychotic ha e ame feela ts'ebetso ea erectile, empa hape e fokotsa libido, e baka ho khutla hape ho fokotsa ho tsosa takatso ea thobalano le khotsofalo e akaretsang ea thobalano. Tlhahlobo ea Cochrane ea morao-rao e hlahlobile menyetla ea ho kenella khahlano le ho se sebetse hantle ka thobalano ho bakuli ka kalafo ea li-antipsychotic mme ea khothaletsa hore ho fetohela olanzapine ho ka ntlafatsa ts'ebetso ea thobalano ho banna le basali. 64. Leha ho le joalo, liphetho tsena li ne li ipapisitse le liteko tse nyane tse bonoang tse bulehileng, mme monyetla o mong ke ho phekola bakuli ba nang le lefu la kelello le ED ka sildenafil, empa hape bopaki bo sa qaqile 64.

Busingcone

Buspirone ke sethethefatsi se tšoenyang maikutlo se nang le lerato le fokolang la ts'ebetso ea thobalano ha se bapisoa le SSRIs hape se ka khutlisa ho hloka thobalano ho amanang le kalafo ea SSRI 65, 66. Buspirone ke agonist ea nakoana ho 5 1 hydroxytryptamine mofuta oa 5A (XNUMX ‐ HT1A receptors), empa buscinone le li-hydroxylmetabolites tse kholo tsa 5 6 le XNUMX ‐ li tlama ho dopamine D3 le D4 li-receptors tse nang le li-affinity tse bapisoang le ho tlama ho 5 ‐ HT1A li-receptors, 'me li sebetsa e le bahanyetsi ka bobeli dopamine D3 le D4 Li-receptors 67. Ts'ebetso ea 5 ‐ HT1A li-receptor ke li-agonists, mohlala 8 ‐ OH ‐ DPAT, e thibela ho kenella ha likhoto literekeng, athe bahanyetsi ba seamohelang sena ba ntlafatsa sephetho se matla sa prooprate e fanoeng ka tšohanyetso ea apomorphine le fluoxetine 68. Ka hona, lerato le fokolang la ts'ebetso ea erectile e bonoang ka busingcone khahlano SSRI e kanna ea hlalosoa le buspirone e sebetsang joaloka mohanyetsi ho 5 ‐ HT1A li-receptors, empa lithuto tse ling li tla hlokoa ho utloisisa ka botlalo mochini o hlahisang phello ea buspirone khahlano SSRI mosebetsing oa erectile.

Lithethefatsi li eketsa dikaiti tsa dopamine ea synaptic

Litaba tsa dopamine tsa synaptic li ka eketsoa ka ho eketsoa ha dopamine, ka ho thibela dopamine reuptake transporter (DAT), kapa ka ho thibela ho phatloha ha dopamine ka thibelo ea catechol‐O‐Methyltransferase (COMT) kapa monoamine oxidase (MAO) mofuta oa mofuta oa inhibitors.

Ho lokolloa ha dopamine

Amantadine

Amantadine ea lithethefatsi tse felisang matla e phahamisa ho lokolloa ha dopamine litsing tsa methapo ea kutlo le ho thibela ho phetoa hape ha dopamine ho neuron ea presynaptic. Ntle le moo, ke mohanyetsi ea fokolang ea N‐Methyl‐dLi-receptors tsa ‐aspartate (NMDA). Leha e na le halofo ea bophelo bo bolelele ba 10-15 hr ho motho, ho nahanoa hore litlamorao e bile tse khuts'oane kaha ho na le nts'etsopele ea mamello ea lithethefatsi. Maemong a 'maloa moo banna le basali ba neng ba phekoloa ka li-anti-depressing, mohlala fluoxetine le paroxetine, ho tlalehiloe hore tlatsetso ea kalafo ka amantadine e khutliselitse ts'oaetso ea thobalano (anorgasm, ED) 10, 69. Leha ho le joalo, liteko tse sa reroang li tla hlokahala ho lekola hore na amantadine e hlile e na le thuso bakeng sa ho khutlisetsa khatello ea thobalano ho bakuli ba tšoaroang ke lingaka tsa khatello ea maikutlo.

Amphetamine le methamphetamine

Oral methamphetamine e sebelisetsoa ho phekola lefu la ho fokola ka hloko le tšebeliso ea litlhare. Ho thoe Amphetamine e tsosa boitšoaro ba thobalano 70. Amphetamine e amahanngoa le ho eketseha ha dopamine, empa le keketseho e eketsehang ea noradrenaline methapong e nang le kutloelo-bohloko e tla lebisa ho constriction ea methapo ea methapo le ea corpus cavernosum 71. Ka hona, tlhekefetso ea methamphetamine le / kapa tšebeliso e sa foleng hangata e lebisa ho ED, phello e ka hlahisoang hape ho litoeba 72. PDE5i, mohlala tadalafil, e ntlafatsa ts'ebetso ea erectile ho likhoto tse tšoaroang ka mokhoa o sa tsitsang ka methamphetamine 72, mme sena se ka hlalosa ts'ebeliso ea boithabiso e kopanyang methamphetamine / amphetamine le tšebeliso ea PDE5i 73, 74.

Clavulanic asiti

Clavulanic acid ke beta ‐ lactamase inhibitor 'me hangata e sebelisoa hammoho le penicillin ho thibela ho senyeha ha penicillin, ka mohlala amoxicillin, ka baktheria beta ‐ lactamase. Clavulanic acid e sebetsa ka molomo ebile e tsitsitse 'me e ka bang 25% e fihla mokelikeli oa "cerebrospinal" ho monna. Ho etsa liteko tsa khale tsa batho tse sa amaneng le clavulanic acid ho fumanoe ho eketsa mohopolo oa thobalano 75, ka hona setlhare se ile sa lekoa likhoto tsa banna tse pepesitsoeng likhoto tsa basali tse tlisitsoeng ho oestrus ea boits'oaro ka ente ea 50 μg estradiol benzoate, mme palo ea li-intromissions le ejaculations e ne e lekantsoe 76. Ho felisa halofo ea bophelo ba clavulanic acid e ka ba hora e le 'ngoe 77, empa e ne e le liketsahalo tse nyane feela tsa thobalano tse matla tse ileng tsa bonoa ka tekanyo e phahameng ka ho fetisisa e fanoeng. Leha ho le joalo, kamora matsatsi a 7 a kalafo, clavulanic acid e ekelitse palo ea li-ejaculations le li-intromissions, ha SSRI, paroxetine, e fokotsa ts'ebetso ea thobalano. 76. Kamoo ho bonahalang kateng, clavulanic acid e ne e sa kopane ho li-receptor tsa "li-neurotransmitter" tsa khale 75, empa ka methapo ea methapo ea methapo ea methapo ea kutlo (PC12 le lisele tsa SH-SY5Y) tse nang le methapo e phahameng ea clavulanic acid (100 μM) e ekelitse tokollo ea dopamine, mohlomong ka ho tlama liprotheine tse peli tsa bohlokoa bakeng sa lipalangoang tsa neurosecretion le vesicle 78. Likhakanyo tse lebelletsoeng tsa cerebrospinal ea clavulanic acid e nang le li-anxiolytic le litlamorao tsa erectile li maemong a 1-10 pM 75. Hore mochine ona o ka bapala karolo o ile oa tšehetsoa hape ke maikutlo a hore dopamine D2 receptor antagonist antagonist the pro ‐ erectile phello ea acid ea clavulanic ho likhoto 79. Thutong ea morao-rao, phello ea asiti ea clavulanic e tsamaisoang ke ente ea intraperitoneal e ile ea bapisoa le apomorphine, mme ha apomorphine e hlohlelletsa keketseho e itšetlehileng ka mahloriso palo ea likhaohano tse itlelang feela, mothinya oa karabelo ea asiti ea clavulanic e ne e entsoe ka tšepe e nang le phello e kholo ho 1 mg / kg ebe e fokotseha ka litekanyetso tse phahameng 80. Bangoli ba khothalelitse hore ntle le ho eketsoa ha dopamine, clavulanic acid e ka eketsa ho lokolloa ha serotonin e sebetsang ho 5 ‐ HT2C li-receptors, joalo ka ha mianserin le eona e hanetsitse phello ea pro ‐ erectile ea clavulanic acid. Boithuto ba karolo ea bobeli bo ne bo reriloe bakeng sa ho lekola katleho ea clavulanic ho bakuli, empa e ile ea emisoa 11. Litaba tse ngata li sa ntsane li lokela ho rarolloa bakeng sa acid ea clavulanic ho kenyelletsa sepheo (s) se amehang phello ea pro-erectile le tlhaloso bakeng sa bell ‐ moetsi oa lethal dose-karolo ea karolo ea clavulanic acid mosebetsing oa erectile.

Thibelo ea dopamine reuptake transporter

Cocaine

Lithethefatsi tse tlatsetsang ho kenyelletsa cocaine ka tloaelo ho nahanoa hore li ntlafatsa dopamine kahare ho moputso oa mesotelencephalic / matlafatso a matla a phatla ea mali, haholo-holo ka har'a li-nucleus 81, empa litsela tse ling tse bonoang ke setšoantšo sa "coson" tsa cortex caudate, putamen, basal forebrain, thalamus, insula, hippocampus, parahippocampal gyrus 82. Ho feta moo, pharmacokinetics le ho kenella ka potlako ho CNS ho bapala karolo ea bohlokoa tlhekefetsong ea koae 83. Cocaine e thibela pele ho "transaptic" ea "transaptic" bakeng sa Noradrenaline (NET), dopamine (DAT) le serotonin (SERT), e leng se eketsang likhopolo tsa synaptic tsa Noradrenaline, dopamine le serotonin. Cocaine e ka eketsa ho tsosa takatso ea botona kapa ea botšehali mme ea lebisa ho penile erection 84, empa tšebeliso e sa tsitsang ea koae e amahanngoa le ED ho monna 85. D1/D5 bahanyetsi ba kang SCH39166 (ecopipam) ba ka fumana litholoana tse matla tsa koae 86. K'hok'heine e sebelisoang haholo ke 'mele ka kotloloho e sitisa ho kenella ho likhoto ka likhoto ka methapo ea methapo ea kutlo, ho kenya li-adrenoceptors ka hippocampus 87. Boemong ba ho potoloha, cocaine ‐ e bakile khatello ea mali ea endothelial le ho eketseha hoa endothelin ‐ 1 mme ea fokotsa nitric oxide le vasoconstriction ho fumanoe ho kenya letsoho ho koaetsoeng ke koae. 85. Liphumano tsena li bonts'a kamano e ntle lipakeng tsa ts'ebetso e tloaelehileng ea erectile ea libaka tsa qoa tsa boko le cocaine bongo brain libaka tse kentsoeng, tse fanang ka maikutlo a hore lithethefatsi tsa ho ntlafatsa ts'ebetso ea erectile ka sephetho sa ho tsamaisa li-monoamine li lokela ho ba le boikhethelo bakeng sa morekisi oa dopamine. Ntle le moo, sethethefatsi ntle le ho qaleha ka potlako ho thibelo ea dopamine ho tlameha ho rereloa ho qoba tlhekefetso joalo ka ha e bonoa cocaine.

Bupropion

Boholo ba li-antidepressants li sebetsa ka tekanyo e fapaneng ho ba tsamaisang li-monoamine. Khetho e phahame bakeng sa thibelo ea SERT ke SSRI, ka mohlala fluoxetine, 'me lithethefatsi tsena li amahanngoa le ho se sebetse ka thobalano. Ho sithabela maikutlo ka bohona ho etsa hore ho be thata ho khetholla phello ea bokuli ho tsoa ho litlamorao tsa lithethefatsi. Mathata a kelello a ka lebisa ho hlokeng thahasello le ho emeng maikutlong ho molekane oa thobalano. Li-antidepressants li ka ba le litlamorao tse ngata mosebetsing oa thobalano ho kenyelletsa takatso e fokotsitsoeng ea thobalano, mathata a erection le mathata a orgasm. SSRI le venlafaxine li ka ama hampe likhato tsohle tsa potoloho ea karabo ea monna (takatso / ho tsosa / thabo). Joalokaha ho akarelelitsoe ho ipapisitsoe le lithuto tse leshome le metso e mehlano tse sa hlophisitsoeng, boipurion, nefazodone le mirtazapine li na le litheko tse tlase tsa khatello ea thobalano ho feta li-SSRIs 9, 88, le bupropion e ka sebelisoa ho fokotsa matšoao a thobalano a bakoang ke litlhare tse ling tsa antidepressant 89, 90. Bupropion hajoale ke eona feela litlatsetso tse felisang mathata ka ho khetheha bakeng sa DAT ho feta NET le SERT ka Ki boleng (nM) ba, ka ho latellana, 526, 52,600 le 9100 bakeng sa batsamaisi ba bararo. Ts'oaetso ea bupropion ho MPOA ka likhoto li eketsehile ka dopamine e lekantsoeng ka micodialysis mme e tsosa li-penile erections ho likhoto 91, empa mohopolo o phahameng haholo (10 mM) oa bupropion o ile oa tlameha ho sebelisoa ho bona phello 91 ho fana ka maikutlo a hore MPOA ha se sebaka sa mantlha moo bupropion e sebetsang kapa hore sethethefatsi nakong ea infusion e matla se kenya tšebetsong litsela tse ling tse khahlanong le erectile. Ho joalo, tsamaiso e matla ea "bupropion" e ile ea fokotsa li-penile erections ka likhoto, ha kalafo ea bupropion matsatsi a 14 (kalafo e sa foleng) e ne e sa amane le liphetoho tsa penile erections ka likhoto, e neng e fapane le kalafo ea fluoxetine kapa desipramine, inhibitor ea NET haholo-holo. 92. Liphumano tsena li fana ka maikutlo a hore ha se feela tekanyetso e phahameng ea "dopamine" e ka har'a synaptic cleft e lekaneng ho hlalosa phello ea pro. Liphetoho likateng tsa dopamine li amahanngoa le polelo e fetotsoeng ea dopamine receptor 35, 93 hape e ka hlalosa ho se tšoane ho litlamorao tse mpe le tse sa foleng tsa tšebetso ea erectile ea bo-ralitima-tšebetso ba bohareng ba ba tsamaisang li-monoamine.

Ho felisoa ha dopamine

Selegiline

Selegiline ke khetho e khethollang, e ke keng ea khutlisoa ea MAO B mme e sebelisoa e le mong kapa e kopane le levodopa kalafong ea lefu la Parkinson. Thibelo ea MAO B e tla liehisa ho senyeha le ho lelefatsa ts'ebetso ea dopamine. Selegiline e feta metabolism ho amphetamine le methamphetamine, e ka tlatsetsang liphellong tsa litlhare ho ts'ebetso ea erectile joalo ka ha ho hlalositsoe kaholimo bakeng sa amphetamine le methamphetamine. Selegiline e ntlafatsa phello ea dopamine ho PVN ho likhoto 94. Ka hona, selegiline kapa koloi e sebelisitsoe libeke tsa 3 bakeng sa kalafo ea ho se sebetse ka thobalano ho bakuli ba kalafo ea antipsychotic thutong e laoloang ea placebo - crossover. Ntle le phokotso ea prolactin e hlohlellelitsoeng ke selegiline, ho ne ho se na phapang mesebetsing ea thobalano ha e bapisoa le nako ea kalafo ea placebo 95.

KatlehoO‐Methyltransferase inhibitors

COMT inhibitors entacapone le tolcapone li sebelisoa e le sehokelo sa levodopa bakeng sa ho senyeha ha tekanyetso ea lefu la Parkinson mme li eketsa ho fumaneha ha levodopa bokong. Ke tolcapone feela e kenang bokong mme e eketsa dopamine ho pre-frontal cortex le ventral hippocampus, empa phello ena e bonahala haholo ho basali ha e bapisoa le likhoto 96. Leha ho le joalo, ha ho tsejoe hore na inhibition ea peripheral COMT le eona e ntseng e eketseha noradrenaline e tla loantšana le phello ea mantlha ea ho eketsa dopamine ts'ebetsong ea thobalano, mme sena se ntse se lokela ho hlakisoa.

Modulation ea dopaminergic pathways le ejaculation

Ha u nahana ka lithethefatsi bakeng sa kalafo ea ED, phello ea ho ejaculation le eona e bohlokoa haholo. Physiology le pharmacology ea ejaculation haufinyane li sa tsoa hlahlojoa haholo 97, 98, 'me mona ke litlhaloso tse khutšoane feela tsa karolo ea litsebo tsa dopaminergic ho ejaculation. Tsela ea incertohypothalamic e kenyelletsang MPOA e bonahala e ameha taolong ea karabelo ea ejaculatory. Maemong ana ka bobeli, keketseho ea litheko tsa dopamine tsa extracellular ho MPOA le ho kenngoa ha apomorphine ho MPOA ho kgutsisa ho koaleha hoa mmele ka palo e eketsehang ea likhahla le lipalo tsa likhoto tsa banna 97. Dopamine D3 receptor e bonahala e bapala karolo ea bohlokoa, joalo ka D2/D3 receptor agonist 7 ‐ hydroxy‐N,N‐Di‐n‐Propyl ‐ 2 ‐ aminotetralin (7 ‐ OH ‐ DPAT) e ntlafatsa boitshwaro ba mmele, ha blockade ea dopamine D3 li-receptors tse nang le bohanyetsi bo ikhethileng bo lelefatsa kemiso ea kemolo le nako ea kamora ‐ 99. Ka hona, D3 bahanyetsi ba li-receptor le bona ba ananetsoe kalafo bakeng sa kemolo ea kemolo pele ho nako 97, leha 7 ‐ OH ‐ DPAT e bonts'itse pholoso e itseng mokhoeng oa ho feto-fetoha hoa mmele ka mokhoa oa ho lemala ho amanang le lesapo la mokokotlo 100. Polymorphism e nang le palo e eketsehang ea ho pheta-pheta ea mofuta oa transporter oa DAT1 e se e khothalelitsoe hore e hokahane le kemolo ea pele ho nako ea motho 101, ha e ntse e sa hlake hantle hore na inhibitor ea DAT, bupropion, litekanyetsong tsa kalafo e ama ejaculation. Dapoxetine le off ‐ label SSRIs li sebetsa hantle ebile li bolokehile bakeng sa kalafo ea kemolo ea peleho, ha e ntse e lula e ntse e hlahlojoa ho monna hore na ho na le phello e ntle ea dopamine D3 bahanyetsi ba receptor. Litsela tse kenyelletsang kemisong ea lintho tsa tlhaho ea tlhaho li ntse li utloisisoa hantle 98, le ho nahana ka lithethefatsi tse fetolang ka kotlolloho tsela ea dopaminergic bakeng sa kalafo ea ED, ho ka ba molemo ho hlahloba le phello ea ho fetoha ha bophelo bo botle le mafu ho netefatsa ts'ebetso ea thobalano ka kakaretso.

Modulation ea Dopaminergic Pathways le Litlhoko Tse sa Hlokoheng ho Bakuli ba nang le bothata ba ho hlobaela ka mmele oa Erectile

Leha ho na le li-inhibitors tsa PDE5 lithethefatsi tse sebetsang, ho ntse ho na le bakuli ba bangata moo kalafo ena e sa lekanang kapa e ka ntlafatsoa ho kenyeletsa bakuli ba nang le lefu la lefu la tsoekere, metabolic syndrome, lefu la neurodegenerative le bakuli ba kileng ba etsa li-prostatectomy tsa radical tse amang methapo ea kutlo. Ho tse latelang, re tsepamisitse maikutlo ho lefu la tsoekere le lefu la neurodegenerative moo re fumanang lithethefatsi tse feto-fetohang litsebe tsa dopaminergic. Maikutlo a mangata mabapi le metabolic syndrome a tšoana le a lefu la tsoekere, ha re ntse re fumana methapo ea methapo mabapi le ramatiki ea kalafo ea methapo kapa ea mothapo oa senya e hloka mekhoa e meng mme sena se rarollotsoe libakeng tse ling. 102.

Lefu la tsoekere le mosebetsi oa erectile

Lefu la tsoekere le amahanngoa le kotsi e kholo ea ED ho feta ho bongata ka kakaretso 103-105. Litliliniking tse phekolang ED, ho ata ha lefu la tsoekere ha comorbidity ke 20-25% 106. Taolo e matla ea glycemic e fokotsa ho ata ha ED 10 lilemo hamorao ho bahlankana ba nang le lefu la tsoekere la mofuta oa 1 107. Leha ho le joalo, ho na le ho haella ha katleho ea li-inhibitors tsa PDE5 ho 50% ea bakuli ba nang le lefu la tsoekere le ED 8, 108-110. Litlhokomeliso tsena li fana ka maikutlo a hore ntle le lerato la litharollo tsa bokhabane tse kenyelletsoeng ho erection, lefu la tsoekere le lona le ama tšebelisano e rarahaneng ea methapo ea kutlo le e ikemetseng e amehang ho kopaneng.

Lerato la lithane tsa erectile le peripheral parasympathetic nerves ho lefu la tsoekere le hlalositsoe hantle. Ka bokhutšoanyane, bothata ba ho se sebetse hantle ha maselese, ho se sebetse hantle ha mesifa le khatello ea kelello li hlalositsoe likoteng tsa lefu la tsoekere le linthong tse ka thoko tse tsoang ho banna ba lefu la tsoekere. 111, 112 (bona Ref. 5). Ho feta moo, hypogonadism e atile haholo ho bakuli ba nang le lefu la tsoekere le ED ha ba bapisoa le ba se nang lefu la tsoekere le ED. Ka lebaka la ho haelloa ke katleho ea li-inhibitors tsa PDE5, tlatsetso ea testosterone hape le lithethefatsi tse lebileng tseleng ea Rho kinase li fumanoe lipatlisiso le ho hlahlojoa ho bakuli ba nang le lefu la tsoekere le lefu la tsoekere. 113-115.

Lerato le nang le lefu la tsoekere la litsela tse bohareng tse kenyang tšebetso ea erectile ha le hlalosoe hantle. Leha ho le joalo, ho ata ha ED ho bakuli ba nang le lefu la tsoekere ho haufi le 100% 116. Litekong tse amanang le lefu la tsoekere ka mokhoa o ikemetseng, rat ea BB / WOR, neuropathies e bohareng le e fumanehang, e fumanoe e amehile ts'ebetsong ea thobalano. 117. Phokotso ea phallo ea methapo ea methapo e khothalelitsoe ho bapala karolo ea nts'etsopele ea neuropathy ea peripheral e amanang le ED 118. Mechini e meng e bonahala e bapala karolo. Ho streptozotocin ‐ mofuta oa 1 le litekanyetso tsa lefu la tsoekere, NMDA ‐ erection e ile ea fuputsoa ka ente e tobileng ho PVN 119. NMDA e hlohlelletsa mekhoa e ts'oanang ea oxytocinergic joalo ka dopamine, mme ho bile le ED le polelo e fokotsehileng ea neuronal NOS ho PVN 119. Bangoli ba fumane hore ho ikoetlisa le ho phekola ka mofuta oa angiotensin II (AT1) bahanyetsi ba li-receptor ba ntlafatsa ts'ebetso ea erectile ho lefu lena la "streoplezocin" 120, 121, empa phello ea lithethefatsi tsa dopaminergic mosebetsing oa erectile e sa ntse e lokela ho hlahlojoa mefuteng ea liphoofolo e nang le lefu la tsoekere.

Ho na le bopaki bo tšehetsang hore lefu la tsoekere le ama tsela e bohareng ea dopaminergic mme le lebisa lefung. Kotsi ea lefu la Parkinson e ne e le ~ 40% e phahameng ho bakuli ba nang le lefu la tsoekere ho feta bakuli ba se nang lefu la tsoekere 122, le ho hanyetsa insulin bokong ba qoqotho ‐ ho kokota ho khethehileng ha insulin receptor induces ho eketsa maemo a mofuta oa monoaminoxidase B, ho eketseha ha dopamine le ho fokotsa ho lokolloa ha dopamine 123. Ho litoeba tse nang le lefu la tsoekere le phahameng, ho na le tahlehelo ea methapo ea methapo 124. Liphumano tsena li fana ka maikutlo a hore lerato la dopaminergic pathways a lefu la tsoekere le lona le ka bapala karolo ea lona ho ED. Leha ho le joalo, ramatiki oa dopaminergic agonist oa mehleng, o bile le ts'usumetso e ts'oanang feela le placebo ho bakuli ba 130 ba nang le lefu la tsoekere le ED, 'me ea arabelang ka mokhoa o tloaelehileng o ne a le monyane a bile a le taolo e ntle ea glycemic 125. Boithuto bo eketsehileng bo tla hlokoa ho utloisisa hore na modulation ea dopaminergic pathways eseng feela bohareng, empa le boemong ba peripheral e ka khutlisa ts'ebetso ea erectile ho lefu la tsoekere.

Lefu la neurodegenerative le dysfunction ea erectile

Litlamorao tsa mafu a methapo ea pelo, lefu la Parkinson le lefu la Alzheimer, mabapi le ho se sebetse ka thobalano le kalafo e khothalelitsoeng li sa tsoa hlahlojoa ke ba bang 126. Ho se sebetse ka thobalano ho atile ho bakuli ba nang le mathata ana, mme ED e nkuoa e le e 'ngoe ea mathata a amanang le ho holofala a amanang le eona 127. PDE5i le apomorphine lia sebetsa ho bakuli ba bangata ba nang le lefu la Parkinson le ED 42, leha ho tla hlokahala litekanyetso tse phahameng haholo ho feta tse khothalletsoang ke apomorphine 127. Joalokaha ho boletsoe mabapi le lithethefatsi tse fapaneng tsa dopaminergic likarolong tse kaholimo, bosodoma bo susumetsoang ke lithethefatsi le bona bo tlameha ho sebetsoa ho fana ka kalafo e nepahetseng ka lithethefatsi tsa dopaminergic lefung la Parkinson.

Liphello le Mehopolo

Re tsepamisitse maikutlo phetoho ea tsela ea dopaminergic bakeng sa kalafo ea ED. Letoto la li-agonists tsa dopaminergic li na le phello mosebetsing oa erectile ka litoeba ka ts'ebetso e bohareng ea dopamine D2Li-receptors tse kang, 'me boholo ba D1Li-receptors tse kang "li-tisy erectile." Fesetere ea kalafo bakeng sa apomorphine e tloaelehileng ea dopamine e tšesaane ebile e sebetsa ho li-receptor tsa dopamine tse bohareng. Ka hona, apomorphine e fumanoe e sa sebetse ho bakuli ba nang le lefu la tsoekere le lefu la tsoekere hape e sa sebetse hantle ha e bapisoa le li-inhibitors tsa PDE5. MiniReview ea hona joale ea lingoliloeng e fana ka maikutlo a hore ho feto-fetoha ha mekhoa ea dopaminergic ho fana ka monyetla oa ho ntlafatsa kalafo ea ED. Leha ho le joalo, sena se ka hloka mokhoa oa ho ngola o tobileng tseleng ea dopaminergic maemong a 'maloa a penile Reflex arch. Ho feta moo, tlhahlobo e tsoelang pele ea lithethefatsi tsa dopaminergic mefuteng ea liphoofolo bakeng sa lefu la tsoekere, metabolic syndrome le / kapa lefu la neurodegenerative e tla ba e loketseng.

Liteboho

Ulf Simonsen ke karolo ea MEMBRANES, Univesithi ea Aarhus, ha Simon Comerma ‐ Steffensen a tšehelitsoe ke phano ea PhD e tsoang Univesithing ea Aarhus.

Khohlano ea Thahasello

Bangoli ba phatlalatsa hore ha ho na likhohlano tsa thahasello.

  1. 1E HLAHETSE KE: Andersson KE. Mekhoa ea ho hlophisoa ha penile le motheo oa kalafo ea litheko tsa methapo ea kutlo erectile. Mofuta oa litlatse Rev 2011;63: 811-59.
  2. 2Monghali Melis MR, Argiolas A. Taolo e bohareng ea ho qaptjoa ha penile: ho etela karolo ea oxytocin le ho sebelisana ha eona le dopamine le glutamic acid ho litoeba tsa banna.. Neurosci Biobehav Rev 2011;35: 939-55.
  3. 3Giuliano F, Bernabe J, Jardin A, Rousseau JP. Karolo ea antirectile ea methapo ea kutloelo-bohloko e nang le kutloelo-bohloko ho likhoto. J Urol 1993;150: 519-24.
  4. 4Moahloli WG, Barba V, Leyba L, Galindo R. Ts'ebetso ea neural le endothelial nitric oxide synthase ho rat penile erectile tishu. Cell Tissue Res 1995;282: 109-16.
  5. 5Gratzke C, Angulo J, Chitaley K, Dai YT, Kim NN, Paick JS et al. Anatomy, physiology, le pathophysiology ea ho se sebetse ha erectile. J Sex Med 2010;7: 445-75.
  6. 6Goldstein I, Jones LA, Belkoff LH, Karlin GS, Bowden CH, Peterson CA et al. Avanafil bakeng sa kalafo ea ho hlohlona ha erectile: multicenterer, randomized, Double ‐ blind blind ho banna ba nang le lefu la tsoekere mellitus. Mayo Clin Proc 2012;87: 843-52.
  7. 7Porst H, Burnett A, Brock G, Ghanem H, Giuliano F, Glina S et al. SOP Conservative (bongaka le tloaelo) kalafo ea dysfunction ea erectile. J Sex Med 2013;10: 130-71.
  8. 8Nehra A, Jackson G, Merafo M, Billups KL, Burnett AL, Buvat J et al. Litlhahiso tsa Princeton III Consensus bakeng sa taolo ea ho hlohlona ha erectile le lefu la pelo. Mayo Clin Proc 2012;87: 766-78.
  9. 9Taylor MJ, Rudkin L, Hawton K. Ho lokile. Maano a ho sebetsana le khatello ea maikutlo ka thobalano: a hlohlelletsa thobalano: boikoetliso bo hlophisehileng ba liteko tse laoloang ka mokhoa o ikhethileng. J Mathata a Khahlano 2005;88: 241-54.
  10. 10Moll JL, CS CS. Ts'ebeliso ea li-pharmacological moemeli ho phekola bothata ba thobalano: bopaki ka har'a lingoliloeng. J Sex Med 2011;8: 956-70.
  11. 11Tlhoro ea TC, Yafi FA, Sangkum P, Hellstrom WJ. Lithethefatsi tse hlahang bakeng sa kalafo ea dysfunction ea erectile. Lithethefatsi Opin Emerg 2015;20: 263-75.
  12. 12Monghali Melis MR, Argiolas A, Gessa GL. Apomorphine ‐ e bakile penile erection le yawning: sebaka sa ts'ebetso bokong. Resin ea Boko 1987;415: 98-104.
  13. 13Argiolas A, Hedlund H. Mofumahali (pharmacology) le tleliniki ea bongaka ea apomorphine SL. BJU Int 2001;88(Suppl 3): 18-21.
  14. 14Argiolas A, Melis MR, Mauri A, Gessa GL. Paraventricular nucleus lesion e thibela ho hohola le penile erection e susumetsoang ke apomorphine le oxytocin empa eseng ke ACTH ka likhoto. Resin ea Boko 1987;421: 349-52.
  15. 15Chen KK, Chan JY, Chang LS. Dopaminergic neurotransication sethaleng sa methapo ea hypothalamus ho tsamaiso ea mantlha ea penile erection ho rat. J Urol 1999;162: 237-42.
  16. 16Hull EM, Muschamp JW, Sato S. Litlhahlobo Dopamine le serotonin: tšusumetso ea boitšoaro ba monna ba thobalano. Physiol Behav 2004;83: 291-307.
  17. 17Bjorklund A, Lindvall O, Nobin A. Bopaki ba ts'ebetso ea ts'ebetso ea methapo ea qoabi ea "hypertalamic" dopamine neurone e ka hara rat. Resin ea Boko 1975;89: 29-42.
  18. 18Skagerberg G, Lindvall O. Mokhatlo oa "diencephalic dopamine neurones" o qala mokokotlo oa lesapo. Resin ea Boko 1985;342: 340-51.
  19. 19Skagerberg G, Bjorklund A, Lindvall O, Schmidt RH. Tšimoloho le ho felisoa ha sisteme ea diencephalo ‐ spinal dopamine ho rat. Brain Res Bull 1982;9: 237-44.
  20. 20Ridet JL, Sandillon F, Rajaofetra N, Geffard M, Sekolo sa A. Sistamin dicaminergic system ea rat: ho ithuta le ho sebelisa microscopic e bobebe le e sebelisang antiserum khahlano le dopamine, haholo ka ts'usumetso ea liketsahalo tsa synaptic. Resin ea Boko 1992;598: 233-41.
  21. 21Holstege JC, Van DH, Buijs RM, Goedknegt H, Gosens T, Bongers CM. Ho ajoa ha dopamine immunoreactivity ho rat, katse le monkey lesapo la mokokotlo. J Comp Neurol 1996;376: 631-52.
  22. 22Van DH, Dijk J, Voom P, Holstege JC. Sebaka sa lehae sa dopamine D2 receptor mokokotlong oa mokokotlo o khetholloang ka immunocytochemistry le in situ hybridization. Eur J Neurosci 1996;8: 621-8.
  23. 23Giuliano F, Allard J. Mosebetsi Dopamine le ts'ebetso ea thobalano ya banna. Eur Urol 2001;40: 601-8.
  24. 24Giuliano F, Allard J, Rampin O, Droupy S, Benoit G, Alexandre L et al. Spinal proerectile phello ea apomorphine ka hara anesthetised rat. Int J Impot Res 2001;13: 110-5.
  25. 25Ho utloa bohloko KJ, Musicki B, Palese MA, Crone JK, Becker RE, Moriarity JL et al. Akt ‐ phosphorylation ‐ ide ide ide ide ide ide oxide synthase ateside ilease. Proc Natl Acad Sci USA 2002;99: 4061-6.
  26. 26Simonsen U, Garcia ‐ Sacristan A, Prieto D. Methapo ea litho tsa penile. J Vasc Res 2002;39: 283-303.
  27. 27Ho hlophisa O, Kun A, Flyvbjerg A, Kirkeby HJ, Jensen JB, Simonsen U. Flow ‐ vasodilation e tsoileng mofets'e e phuthulitsoe ka methapo ea methapo e tsoang ho mafura a Zucker a tsoekere a mafura. J Sex Med 2012;9: 1789-800.
  28. 28Lue TF, Tanagho EA. Physology ea erection le pharmacological taolo ea ho hloka matla. J Urol 1987;137: 829-36.
  29. 29El ‐ Din MM, Senbel AM, Daabees TT, Sharabi FM. Ho feto-fetoha ha molumo oa li-receptor tsa dopaminergic ho ama likarabo tsa erectile ho likhoto. Motsoako oa mantlha oa Clinic Pharmacol 2007;100: 225-32.
  30. 30Hyun JS, Bivalacqua TJ, Baig MR, Yang DY, Leungwattanakij S, Abdel ‐ Mageed A et al. Localization of peripheral dopamine D1 le D2 receptors ho rat Corpus cavernosum. BJU Int 2002;90: 105-12.
  31. 31d'Emmanuele di Villa Bianca R, Sorrentino R, Roviezzo F, Imbimbo C, Palmieri A, De Dominicis G et al. Ketsahalong e khathollang ea apomorphine le ngaka e ikhethileng e amohelang li-receptor receptor agrest ea motho.. Int J Impot Res 2005;17: 127-33.
  32. 32Han DH, Chae MR, ke 'na, Park JK, Lee SW. Litlamorao tsa li-dopamine receptor agonists liteisheneng tsa BK Ca le mochine oa phetisetso ea li-cell liseleng tse bonolo tsa mesifa. Int J Impot Res 2008;20: 53-9.
  33. 33Mignini F, Traini E, Tomassoni D, Amenta F. Keletso Dopamine plasma membrane transporter (DAT) ho rat thymus le spleen: thuto ea immunochemical and immunohistochemical. Auton Autacoid Pharmacol 2006;26: 183-9.
  34. 34Pfeil U, Kuncova J, Bsiansmann D, Paddenberg R, Rafiq A, Henrich M et al. Intrinsic vascular dopamine - senotlolo sa senotlolo sa hypoxia ‐ se kentseng vasodilatation likepeng tsa splanchnic. J Physiol 2014;592: 1745-56.
  35. 35Beaulieu JM, Espinoza S, Gainetdinov RR. Li-receptor tsa Dopamine - Tlhahlobo ea IUPHAR 13. Br J Pharmacol 2015;172: 1-23.
  36. 36Kebabian JW. Mekhahlelo e mengata ea li-receptor tsa dopamine tsamaisong ea methapo ea methapo ea mali: ho nka karolo ha dopamine. Bophelo ba Saense 1978;23: 479-83.
  37. 37Heaton JP Lintlha tsa bohlokoa tse tsoang litekong tsa kliniki tsa apomorphine SL. Lefatshe J Urol 2001;19: 25-31.
  38. 38Hsieh GC, Hollingsworth PR, Martino B, Chang R, Terranova MA, O'Neill AB et al. Mechine e bohareng e tataisang kemaro ea penile ho litoeba tse tlhokomelitsoeng: litsamaiso tsa dopaminergic tse amanang le phello ea proerectile ea apomorphine. J Pharmacol Exp Ther 2004;308: 330-8.
  39. 39Baskerville TA, Douglas AJ. Tšebelisano pakeng tsa dopamine le oxytocin taolong ea boitšoaro ba thobalano. Prog Brain Res 2008;170: 277-90.
  40. 40Matsumoto K, Yoshida M, Andersson KE, Hedlund P. Liphello in vitro le in vivo ka apomorphine ho rat corpus cavernosum. Br J Pharmacol 2005;146: 259-67.
  41. 41Heaton JP, Morales A, Adams MA, Johnston B, el Rashidy R. Pholoso ea ts'ebetso ea erectile ke tsamaiso ea molomo ea apomorphine. Urology 1995;45: 200-6.
  42. 42Heaton JP, Altwein JE. Karolo ea apomorphine SL kalafo ea dysfunction ea banna. BJU Int 2001;88(Suppl 3): 36-8.
  43. 43Maclennan KM, Boshier A, Wilton LV, Shakir SA. Teko ea polokeho le tšebeliso ea apomorphine e laetsoeng ho sebelisoa ka kakaretso England e le kalafo bakeng sa ho se sebetse hantle ha erectile. BJU Int 2006;98: 125-31.
  44. 44Schulze A, Oehler B, Urban N, Schaefer M, Hill K Apomorphine ke bimodal modulator ea liteishene tsa TRPA1. Mol Pharmacol 2013;83: 542-51.
  45. 45Sebele AM. Tšebelisano lipakeng tsa nitric oxide le phetisetso ea dopaminergic taolong ea paripheral ea erection ea penile. Fundam Clin Pharmacol 2011;25: 63-71.
  46. 46Sharifzadeh M, Dehpour AR, Samini M, Hassan ‐ Mazandarani H, Samadian T, Asghari GR. Liphetoho tsa bromocriptine ‐ e bakile penile erection ka lithium e sa foleng ho likhoto. J Psychopharmacol 1996;10: 157-61.
  47. 47Baskerville TA, Allard J, Wayman C, Douglas AJ. Dopamine-oxytocin o sebetsana le penile erection. Eur J Neurosci 2009;30: 2151-64.
  48. 48Radosavljevic M, Pajovic B, Radunovic M, Radojevic N, Bjelogrlic B. Ho hlakile Tšusumetso ea dihydroergotoxine, bromocriptine, le ergotamine ho erection ea penile ho likhoto tsa Wistar. J Androl 2012;33: 866-71.
  49. 49Le FB, Collo G, Rabiner EA, Boileau I, Merlo PE, Sokoloff P. Dopamine D3 receptor ligands bakeng sa kalafo ea ts'ebeliso ea lithethefatsi: ntlafatso liphumantsong tsa morao-rao. Prog Brain Res 2014;211: 255-75.
  50. 50Sokoloff P, Diaz J, Le FB, Guillin O, Leriche L, Bezard E et al. Dopamine D3 receptor: sepheo sa phekolo bakeng sa kalafo ea mathata a amanang le neuropsychiatric. Lits'ebetso tsa lithethefatsi tsa CNS Neurol Disord 2006;5: 25-43.
  51. 51De La Peña Zarzuelo E, Hernández Cañas V, Llorente AC. [Priapism ea bobeli kalafo e hlahang ka lebaka la k'habeche: tlhaloso ea pele ea mokhatlo ona]. Actas Urol Esp 2010;34: 487-8.
  52. 52Cannas A, Meloni M, Mascia MM, Solla P, Orofino G, Farris R et al. Ho tsepamisa mohopolo le hypersexourse e amanang le rotigotine ho mokuli ea seng a tsofetse oa parkinsonian: tlaleho ea nyeoe. Clin Neuropharmacol 2016;39: 162-3.
  53. 53Spagnul SJ, Cabral PH, Verndl DO, Glina S. Ho hlakile Adrenergic alpha ‐ blockers: sesosa sa maemo le se sa tsotelleng sa ho ikemela. Int J Impot Res 2011;23: 95-8.
  54. 54Worthington JJ III, Simone NM, Korbly NB, Perlis RH, Pollack MH. Ropinirole bakeng sa antidepressant ‐ e entse hore motho a se sebetse ka thobalano. Int Clin Psychopharmacol 2002;17: 307-10.
  55. 55Melis MR, Succu S, Sanna F, Melis T, Mascia MS, Enguehard ‐ Gueiffier C et al. PIP3EA le PD ‐ 168077, li-agonists tse peli tse khethiloeng tsa d4amine receptor agonists, li kenya letsoho ho kenella litekong tsa banna: sebaka le mokhoa oa ts'ebetso bokong. Eur J Neurosci 2006;24: 2021-30.
  56. 56Melis MR, Succu S, MS ea Mascia, Argiolas A. PD ‐ 168077, dopamine e khethang dopamine D4 receptor agonist, e etsa hore penile erection ha e kenngoa khubung ea paraventricular ea likhoto tsa banna.. Neurosci Lett 2005;379: 59-62.
  57. 57Brioni JD, Moreland RB, Cowart M, Hsieh GC, Stewart AO, Hedlund P et al. Ho kenngwa tshebetsong ha dopamine D4 receptors ke ABT ‐ 724 ho kenya penre erection ho likhoto. Proc Natl Acad Sci USA 2004;101: 6758-63.
  58. 58Patel MV, Kolasa T, Mortell K, Matulenko MA, Hakeem AA, Rohde JJ et al. Discovery of 3 ‐ methyl‐N- (1 ‐ oxe ‐ 3 ′, 4 ′, 5 ′, 6'‐ tetrahydro ‐ 2'H‐ [2,4' ‐ bipyridine] ‐1 ‐ ylmethyl) benzam ide (ABT ‐ 670), dopamine ea molomo e fumanehang ka molomo. D4 agonist bakeng sa kalafo ea ho hlohlona ha erectile. J Med Chem 2006;49: 7450-65.
  59. 59Meador ‐ Woodruff JH, Mansour A, Grandy DK, Damask SP, Civelli O, Watson SJ Jr. Ho tsamaisoa ha D5 dopamine receptor mRNA bokong ba rat. Neurosci Lett 1992;145: 209-12.
  60. 60Khan ZU, Gutierrez A, Martin R, Penafiel A, Rivera A, oa la Calle A. Dopamine D5 li-receptors tsa rat le boko ba motho. Khopolo-taba 2000;100: 689-99.
  61. 61Kudwa AE, Dominguez ‐ Salazar E, Cabrera DM, Sibley DR, Rissman EF. Dopamine D5 receptor modulates boits'oaro ba botona le botšehali ho litoeba. Psychopharmacology 2005;180: 206-14.
  62. 62Mocha oa SL, Taylor M, Lawrie SM. "Pele u se ke oa senya". Tlhahlobo e hlophisehileng ea ho ata le taolo ea litla-morao tse matla tsa antipsychotic. J Psychopharmacol 2015;29: 353-62.
  63. 63Jeong HG, Lee MS, Lee HY, Ko YH, Han C, Joe SH. Liphetoho ts'ebetsong ea thobalano le li-hormone tsa gonadal axis kamora ho fetohela ho aripiprazole ho bakuli ba schizophrenia ea banna: thuto e tlang ho ba ea sefofane. Int Clin Psychopharmacol 2012;27: 177-83.
  64. 64Schmidt HM, Hagen M, Kriston L, Soares ‐ Weiser K, Maayan N, Berner MM. Tsamaiso ea khatello ea kelello ho tsa thobalano ka lebaka la kalafo ea lithethefatsi tsa antipsychotic. Cochrane Database Syst Rev 2012;11: CD003546.
  65. 65Mobu M, Eriksson E, Agren H, Fahlen T. Kameho ea buspirone ho sebetsanang le thobalano ho bakuli ba sithabetseng ba phekoloang ka li-inhibitors tse khethiloeng tsa serotonin. J Clinic Psychopharmacol 1999;19: 268-71.
  66. 66Mobu M, Bjorling G, Agren H, Fahlen T. Teko e laoloang ka tšohanyetso ea batho ba sa sebetseng, ba sa boneng mahlakore a mabeli a sa bonahaleng, sebakeng sa bolulo, e sebelisitsoeng hammoho le SSRI ho bakuli ba nang le kalafo.. J Clinic Psychiatry 1998;59: 664-8.
  67. 67Bergman J, Marulelo RA, Furman CA, Conroy JL, Mello NK, Sibley DR et al. Ho hlophisoa ha tsamaiso ea koae ka "cocaine" ka busecone (buspar (R)): D3 le D4 dopamine receptors. Int J Neuropsychopharmacol 2013;16: 445-58.
  68. 68Protais P, Windsor M, Mocaer E, Comoy E Post ‐ synaptic 5 ‐ HT1A receptor ho kenya letsoho ho hlohlona le ho kenella ha li-penile ho hlohlellelitsoeng ke apomorphine, physostigmine le mCPP ka litoeba. Psychopharmacology 1995;120: 376-83.
  69. 69Balogh S, Hendricks SE, Kang J. Phekolo ea fluoxetine ‐ e hlahisitse anorgasmia le amantadine. J Clinic Psychiatry 1992;53: 212-3.
  70. 70Angrist B, Gershon S. Litlamorao tsa tleleniki ea amphetamine le L ‐ DOPA litabeng tsa thobalano le mabifi. Compr Psychiatry 1976;17: 715-22.
  71. 71Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI et al. Amphetamine ‐ mofuta oa methapo e matla ea methapo e hlahisang norepinephrine ka mokhoa o matla ho feta ha ba lokolla dopamine le serotonin. Synapse 2001;39: 32-41.
  72. 72Tar MT, Martinez LR, Nosanchuk JD, Davies KP. Matla a methamphetamine mohlaleng oa phoofolo ea mosebetsi oa erectile. Andrology 2014;2: 531-6.
  73. 73Mansergh G, Shouse RL, Mareka G, Guzman R, Rader M, Buchbinder S et al. Tšebeliso ea Methamphetamine le sildenafil (Viagra) li hokahanngoa le thobalano e amohelang e sa sireletsehang ea ho kopanela liphate, ka ho tšoanang, mohlaleng oa banna ba etsang thobalano le banna. Tšoaetso ea Transm 2006;82: 131-4.
  74. 74Boemo ba G, Jin F, Kippax S, Zablotska I, Imrie J, Grulich A. Tšebeliso ea lithethefatsi tse seng molaong le meriana ea ho itlosa bolutu ka HIV le tšoaetso e latelang ea HIV har'a banna ba ratanang le ba bong bo tona ba Sydney, Australia. J Sex Med 2009;6: 2311-20.
  75. 75Kim DJ, King JA, Zuccarelli L, Ferris CF, Koppel GA, Snowdon C. et al. Clavulanic acid: inhibitor ea beta ‐ lactamases e nang le mofuta oa ho ts'oenyeha ka mofuta oa "mesebetsi" le litla-morao tse fokolang.. Pharmacol Biochem Behav 2009;93: 112-20.
  76. 76Chan JS, Kim DJ, Ahn CH, Ho eketsa RS, Olivier B. Clavulanic acid e matlafatsa boitšoaro ba thobalano ho likhoto tsa banna. Eur J Pharmacol 2009;609: 69-73.
  77. 77Nakagawa H, Yamada M, Tokiyoshi K, Miyawaki Y, Kanayama T. [Ho kenella hoa potasiamo ea potasiamo clavulanate / ticarcillin sodium ho mokelikeli oa "cerebrospinal" ho bakuli ba neurosuction]. Jpn J Lithibela-mafu 1994;47: 93-101.
  78. 78Kost GC, Selvaraj S, Lee YB, Kim DJ, Ahn CH, Singh BB. Clavulanic acid e eketsa tlhahiso ea dopamine liseleng tsa neuronal ka mochine o kenyelletsang ts'ebetso ea vesicle e ntlafalitsoeng. Neurosci Lett 2011;504: 170-5.
  79. 79Sanna F, Succu S, Hubner H, Gmeiner P, Argiolas A, Melis Monghali. Dopamine D2 ‐ joalo ka li-receptor agonists li kenya letsoho ho kenella litekong tsa banna: karolo e khethollang ea D2, D3 le li-D4 receptors karolong e khutsitseng ea hypothalamus. Behav Brain Res 2011;225: 169-76.
  80. 80Sanna F, Melis MR, Angioni L, Argiolas A. Clavulanic acid e etsa hore ho be le penile erection le ho hlohlona ka likhoto tsa banna: ho bapisoa le apomorphine. Pharmacol Biochem Behav 2013;103: 750-5.
  81. 81Robinson TE, Berridge KC. Motheo oa neural oa takatso ea lithethefatsi: mohopolo oa tšusumetso ea ho lemalla. Brain Res Brain Res Rev 1993;18: 247-91.
  82. 82Moferefere HC, Gollub RL, Weisskoff RM, Kennedy DN, Makris N, Berke JD et al. Litlamorao tse mpe tsa cocaine tšebetsong ea kelello ea motho le maikutlo a hae. Neuron 1997;19: 591-611.
  83. 83Chow HS, Chen Z, Matsuura GT. Tsamaiso ea koae ka kotloloho ho tsoa molomong oa nko ho ea bokong ho latela ts'ebetso ea "cocaine" ea "cocaine" lipakeng. J Pharm Sci 1999;88: 754-8.
  84. 84Mookameli LL, Mark H. Mathata a bongaka a tlhekefetso ea koae. N Engl J Med 1986;315: 1495-500.
  85. 85Kendirci M, Pradhan L, Trost L, Gur S, Chandra S, Agrawal KC et al. Mekhoa e poteletseng ea ho se sebetse hantle ha erectile dysfunction ho rat ea cocaine e sa foleng. Eur Urol 2007;52: 555-63.
  86. 86Romach MK, Glue P, Kampman K, Kaplan HL, Somer GR, Poole S et al. Khokahano ea litlamorao tsa cocaine ea dopamine D1 / D5 antagonist ecopipam (SCH 39166). Arch Gen Psychiatry 1999;56: 1101-6.
  87. 87Chang AY, Chan JY, Chen SH. Hippocampal noradrenergic neurotransuction in concynchronization ea EEG e kopanetsoeng le thibelo ea penile erection e hlahisoang ke koae ho lere. Br J Pharmacol 2000;130: 1553-60.
  88. 88Coleman CC, King BR, Bolden ‐ Watson C, Book MJ, Segraves RT, Richard N et al. Papiso e laoloang ea placebo ‐ ea litlamorao tsa ts'ebetso ea thobalano ea lupropion e lokolloang le fluoxetine. Clin Ther 2001;23: 1040-58.
  89. 89Gitlin MJ, Suri R, Altshuler L, Zuckerbrow ‐ Miller J, Fairbanks L. Bupropion release tokollo e tsitsitseng e le kalafo bakeng sa litlamorao tsa thobalano tsa SSRI. J Ther ea lenyalo 2002;28: 131-8.
  90. 90Taylor MJ, Rudkin L, Bullemor ‐ Day P, Lubin J, Chukwujekwu C, Hawton K. Maano a ho sebetsana le ho se sebetse hantle ka thobalano a khothalletsoang ke meriana ea litlhare. Cochrane Database Syst Rev 2013;5: CD003382.
  91. 91Adachi H, Sato Y, Kato R, Hisasue S, Suzuki K, Masumori N et al. Bopaki bo tobileng ba liketso tse tataisang tsa dopamine tikolohong ea medial preoptic mabapi le li-erections tse sa hlakang le tse sa amaneng le likhoto tsa banna. J Urol 2003;169: 386-9.
  92. 92Sukoff Rizzo SJ, Schechter LE, Rosenzweig ‐ Lipson S. Mokhoa o mocha oa ho bolela esale pele antidepressant ‐ o entse hore ho se sebetse thobalanong ho litoeba. Psychopharmacology 2008;195: 459-67.
  93. 93Beaulieu JM, Gainetdinov RR (Khatisitsoeng) Physiology, signaling, le pharmacology ea dopamine receptors. Mofuta oa litlatse Rev 2011;63: 182-217.
  94. 94Allard J, Bernabe J, Derdinger F, Alexandre L, McKenna K, Giuliano F. Seboka Selegiline e ntlafatsa ts'ebetso ea erectile e hlahisoang ke ente ea dopamine sebakeng sa "patothricular nucleus" ea hypothalamus ho likhoto tse sa sebetseng. Int J Impot Res 2002;14: 518-22.
  95. 95Kodesh A, Weizman A, Aizenberg D, Hermesh H, Gelkopf M, Zemishlany Z. Ho lokolloa Selegiline kalafo ea ho hlobaela ka thobalano ho bakuli ba schizophrenic ba lulang ho li-neuroleptics: thuto ea sefofane. Clin Neuropharmacol 2003;26: 193-5.
  96. 96Laatikainen LM, Sharp T, Harrison PJ, Tunbridge EM. Litaba tsa thobalano le catechol‐O‐Methyltransferase (COMT) inhibition ho dopamine metabolism libakeng tse ngata tsa boko. PLoS ONE 2013;8: e61839.
  97. 97Giuliano F, Clement P. Pharmacology bakeng sa kalafo ea kemolo ea peleho. Mofuta oa litlatse Rev 2012;64: 621-44.
  98. 98Clement P, Giuliano F. Physology le pharmacology ea ejaculation. Motsoako oa mantlha oa Clinic Pharmacol 2015; Doi: 10.1111 / bcpt.12546.
  99. 99Clement P, Pozzato C, Heidbreder C, Alexandre L, Giuliano F, Melotto S. Sebopeho Ho lieha hoa ejaculation e susumetsoang ke SB ‐ 277011, mohanyetsi oa dopamine D3 receptor antagonist, ho rat. J Sex Med 2009;6: 980-8.
  100. 100Kozyrev N, Staudt MD, brown A, Coolen LM. Bohloko bo sa feleng bo amanang le lesapo la mokokotlo bo sitisa methapo ea kutlo ho litoeba tsa banna: ho hlaphoheloa ka nakoana ke infusions ea dopamine D3 receptor agonist 7OHDPAT. J Neurotrauma 2016;33: 943-53.
  101. 101MOTSOALLE MOR. Kamano lipakeng tsa ejaculation ea pele ho nako le li-polymorphisms tsa liphatsa tsa lefutso tsa dopamine transporter (SLC6A3). BJU Int 2011;108: 292-6.
  102. 102El ‐ Sakka AI. Karolo ea hona joale ea ente ea intracavernosal ho tsamaisa ho senyeha ha erectile ke efe? Int J Impot Res 2016;28: 88-95.
  103. 103Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ, McKinlay JB. Matlafatso le tlhabollo ea eona ea bongaka le kelello: litlamorao tsa Massachusetts Male Aging Study. J Urol 1994;151: 54-61.
  104. 104Johannes CB, Araujo AB, Feldman HA, Derby CA, Kleinman KP, McKinlay JB. Ketsahalo ea ho se sebetse ha erectile ho banna ba lilemo li 40 ho isa ho tse 69: liphetho tsa bolelele ba nako ho tsoa boithutong ba botsofali ba banna ba Massachusetts. J Urol 2000;163: 460-3.
  105. 105Martin ‐ Morales A, Sanchez ‐ Cruz JJ, Saenz de Tejada I, Rodriguez ‐ Vela L, Jimenez ‐ Cruz JF, Burgos ‐ Rodriguez R. Lisosa le likotsi tse ikemetseng tsa ho senyeha ha erectile Spain: Liphetho tsa thuto ea Epidemiologia de la Disfuncion Erectil Masculina. J Urol 2001;166: 569-74.
  106. 106Sairam K, Kulinskaya E, Boustead GB, Hanbury DC, McNicholas TA. Ho ba teng ha tsoekere e sa tsejoang ea lefu la tsoekere ho dysfunction ea banna. BJU Int 2001;88: 68-71.
  107. 107Wessell H, Penson DF, Cleary P, Rutledge BN, Lachin JM, McVary KT et al. Matla a kalafo e matla ea glycemic ts'ebetsong ea erectile ho banna ba nang le lefu la tsoekere la 1. J Urol 2011;185: 1828-34.
  108. 108Behrend L, Vibe ‐ Petersen J, Perrild H. Sildenafil kalafo ea ho hlobaela ha erectile ho banna ba nang le lefu la tsoekere: tlhoko, katleho le khotsofalo ea mokuli. Int J Impot Res 2005;17: 264-9.
  109. 109Israilov S, Shmuely J, Niv E, Engelstein D, Livne P, Boniel J. Mosebetsi Tlhahlobo ea lenaneo le tsoelang pele la kalafo bakeng sa ho se sebetse hantle ha erectile ho bakuli ba nang le lefu la tsoekere. Int J Impot Res 2005;17: 431-6.
  110. 110Porst H, Gacci M, Buttner H, Henneges C, Boess F. Kopano Tadalafil hang ka letsatsi ho banna ba nang le bothata ba ho se sebetse hantle ka mokhoa oa ho se sebetse hantle ka botlalo: tlhahlobo e kopantsoeng ea data e fumanoang ho bakuli ba 1913 ho tsoa ho tse tšeletseng tse sa sebetseng, tse sa boneng mahlo ka bobeli, tsa placebo ‐ tse laoloang.. Eur Urol 2014;65: 455-64.
  111. 111Saenz de Tejada I, Goldstein I, Azadzoi K, Krane RJ, Cohen RA. Ho phomola ha mesifa ea penile boreleli ho tsoa ho banna ba nang le lefu la tsoekere ba sa foleng.. N Engl J Med 1989;320: 1025-30.
  112. 112Xie D, Odronic SI, Wu F, Pippen A, Donatucci CF, Sehlomathiso BH. Moetso oa panya ea ho se sebetse hantle ha erectile ka lebaka la phepelo ‐ e bakang lefu la tsoekere. Urology 2007;70: 196-201.
  113. 113Sopko NA, Hannan JL, Bivalacqua TJ. Ho utloisisa le ho lebisa tseleng ea Rho kinase ka mokhoa oa ho se sebetse ha erectile. Nat Rev Urol 2014;11: 622-8.
  114. 114Corona G, Mannucci E, Petrone L, Ricca V, Balercia G, Mansani R et al. Mokhatlo oa hypogonadism le lefu la tsoekere la mofuta oa II ho banna ba tlileng tliliniking ea diketso tsa mmele tsa nakong e fetileng. Int J Impot Res 2006;18: 190-7.
  115. 115Gur S, Peak TC, Kadowitz PJ, Sikka SC, Hellstrom WJ. Tlhahlobo ea ho se sebetse hantle ha erectile mefuteng ea liphoofolo tse tsoekere. Revr Lefu la Tsoekere 2014;10: 61-73.
  116. 116Matfin G, Jawa A, Fonseca VA. Ho se sebetse hantle ka mokhoa oa Edrectile: ho hokahana le metabolism. Mofani oa Diab ea Curr 2005;5: 64-9.
  117. 117McVary KT, Rathnau CH, McKenna KE. Ho se sebetse ka thobalano ho "lefu la tsoekere" la BB / WOR: karolo ea karolo ea methapo. Ke J Physiol 1997;272: R259-67.
  118. 118Cellek S, Cameron NE, Cotter MA, Muneer A. Pathophysiology ea lefu la tsoekere la lefu la tsoekere: tlatsetso e ka hlahisang vasa amanorum le endproducts e tsoetseng pele ea glycation. Int J Impot Res 2013;25: 1-6.
  119. 119Zheng H, Bidasee KR, Mayhan WG, Patel KP. Ho haella ha nitric oxide e bohareng ho hlohlelletsa ho se sebetse hantle ha lefu la tsoekere. Am J Physiol Regul Compact Comp Comp Physiol 2007;292: R1158-64.
  120. 120Zheng H, Liu X, Patel KP. Ho hloka kutloisiso ho akaretsang ha erectile ho se sebetsane ka likhoto tse nang le lefu la tsoekere 1: karolo ea angiotensin II le superoxide. J Sex Med 2013;10: 2165-76.
  121. 121Zheng H, Mayhan WG, Patel KP. Koetliso ea boikoetliso e ntlafatsa likarabo tse sa nepahalang tsa bohareng ba erectile ka likhoto tse nang le lefu la tsoekere la mofuta oa. J Sex Med 2011;8: 3086-97.
  122. 122Xu Q, Paka Y, Huang X, Hollenbeck A, Blair A, Schatzkin A. et al. Lefu la tsoekere le kotsi ea lefu la Parkinson. Tlhokomelo ea lefu la tsoekere 2011;34: 910-5.
  123. 123Basebetsi ba Kleinridders A, Cai W, Cappellucci L, Ghazarian A, Collins WR, Vienberg SG et al. Ho hanyetsa insulin ho li-brain alters dopamine ho fetoha le ho baka mathata a boitšoaro. Proc Natl Acad Sci USA 2015;112: 3463-8.
  124. 124Khang R, Park C, Shin JH. Ts'oaetso ea Parkin kahara nigra ea db / db le litoeba tse phahameng tsa phepo e phahameng.. Khopolo-taba 2015;294: 182-92.
  125. 125Gontero P, D'Antonio R, Pretti G, Fontana F, Panella M, Kocjancic E et al. Teknoloji e sebetsang ea Clomical ea apomorphine SL ho erectile dysfunction ea banna ba tsoekere. Int J Impot Res 2005;17: 80-5.
  126. 126Bronner G, Aharon ‐ Peretz J, Hassin ‐ Baer S. Ho kopanela liphate ho bakuli ba nang le lefu la Parkinson, lefu la Alzheimer le mafu a mang a 'dementia'. Handb Clin Neurol 2015;130: 297-323.
  127. 127Bronner G, Vodusek DB. Tsamaiso ea ho se sebetse ka thobalano lefung la Parkinson. Ther Adv Neurol Khatello 2011;4: 375-83.