Meriana ea glutamatergic bakeng sa phekolo ea meriana ea lithethefatsi le ea boitšoaro (2013)

inahaneloang

Ho tloha khale, mekhoa e mengata ea kalafo ea kalafo ea mathata a lemalloang e sebelisitse mekhoa e meng e kenang (ke hore, phetoho ea nicotine kapa tlhokomelo ea opioid) kapa e shebile monoaminergic kapa endogenous opioidergic neurotransmitter. Leha ho le joalo, bopaki bo bongata bo bokelletse bo bonts'ang hore li-ligand tse sebelisang phetisetso ea glutamatergic le tsona li na le thuso ho phekoleng bokhoba ba lithethefatsi, hammoho le litloaelo tse fapaneng tsa boits'oaro tse joalo ka papali ea chelete ea papali ea chelete.. Morero oa tlhahlobo ena ke ho akaretsa mekhoa ea ts'ebetso ea litlhare le ts'ebetso e akaretsang ea kalafo ea meriana ea glutamatergic eo hona joale e amoheloang kapa e ntseng e phenyekolloa bakeng sa tumello bakeng sa kalafo ea mafu a lemalloang. Meriana e nang le litlamorao phetisong ea glutamatergic e tla tšohloa e kenyelletsa acamprosate, N-acetylcysteine, D-cycloserine, gabapentin, lamotrigine, memantine, modafinil le topiramate. Re fihlela qeto ea hore ho qhekella ha glutamatergic neurotransmission ho batla ho le nyane empa ho ts'episa mokhoa oa nts'etsopele ea kalafo e ntlafetseng ea kalafo ea lithethefatsi le boits'oaro.

Keywords: ho lemalla lithethefatsi, tšebeliso e mpe ea lithethefatsi, ho lemalla boitšoaro, papali ea chelete, kalafo ea litlama, glutamate

1. Selelekela

Bokhoba ba lithethefatsi, bo hlalositsoeng ke American Psychiatric Association joalo ka tšebeliso ea lithethefatsi (Mokhatlo oa Mahlale oa Amerika, 2002), e na le lipontšo tse ngata tse mpe tsa kelello le boits'oaro tse kenyeletsang: tahlehelo ea taolo ea tšebeliso ea lithethefatsi, ho sebelisa lithethefatsi ka bongata ho feta kamoo ho neng ho reriloe, liteko tse sa atleheng khafetsa tsa ho tlohela kapa ho fokotsa ts'ebeliso ea lithethefatsi, ts'ebeliso e tsoelang pele ea lithethefatsi leha ho na le litlamorao tse mpe, le ho hlaha ha matšoao a mamello le / kapa ho tlohela. Ho tlatselletsa linthong tse ngata tse sa tšoareheng tsa botho tse kang ho senyeha ha malapa le likamano pakeng tsa batho, ho se sebetse sechabeng, le ho lahleheloa ke bophelo, moroalo oa moruo le moruo oo lithethefatsi li o behang sechabeng o matla haholo (Cartwright, 2008; Gilson le Kreis, 2009; Malliarakis le Lucey, 2007; Rehm et al a., 2009; Spanagel, 2009; Khloe et al a., 2009). Lilemong tsa morao tjena ho totobetse hore likaroloana tsa methapo ea kutlo tse lemaletseng lithethefatsi li hlekefetsoa haholo le tsa lithethefatso tse seng tsa "boitšoaro" (ke hore, papali ea chelete, ho shebella litšoantšo tsa bootsoa / ho lemalla inthanete, jj.) (Grant et al a., 2010a).

Ho fihla joale, meriana e ntlafalitsoeng ho thusa kalafong ea mathata a lemalloang e bonts'itse katleho e itekanetseng feela. Lithibelo tse tsebahalang tse sitisang katleho ea mekhoa ea kalafo e sebetsanang le kalafo ea mathata a ho lemalla lithethefatsi li kenyelletsa tšebeliso e mpe ea meriana, litlamorao tse mpe, mathata a polokeho, likarabo tse fapaneng tsa meriana lihlopheng tsa kalafo, kopanyo e mpe ea taolo ea meriana kalafong ea kelello le boits'oaro, ho se fihlellehe. meriana kapa tlhokomelo e lekaneng ea bophelo bo botle, le ho khutlela mokhoeng kamora ho emisa kalafo ea kalafo (Koob et al a., 2009; Montoya le Vocci, 2008; O'Brien, 2008; Ross le Peselow, 2009; Zahm, 2010). Le ha meriana e mengata ea lihlopha tse fapaneng e amohetsoeng bakeng sa maemo a mang a bongaka e ntse e phenyekolloa e le lithuso tse ka bang teng ho phekoleng mafu a lemalloang, meriana e le 'ngoe feela e amoheloang ka kotloloho bakeng sa kalafo ho fihlela joale United States ke varenicline, buproprion, le nicotine mekhoa ea kalafo ea ho emisa ho tsuba, li-opioid tse sebetsang nako e telele (ke hore, methadone kapa buprenorphrine) bakeng sa ts'ebeliso ea opiate, le disulfiram, naltrexone, le acamprosate bakeng sa ts'ebeliso ea joala. Ha ho na meriana e thusang kalafong ea bokhoba ba koae, methamphetamine, kapa matekoane e amoheloang hajoale, ebile ha e lumelloe bakeng sa kalafo ea lithethefatsi.

Morero oa tlhahlobo ea hajoale ke ho fana ka kakaretso ea mekhoa ea ts'ebetso ea litlhare le ts'ebetso e akaretsang ea bongaka ea meriana e sebetsanang le phetisetso ea glutamatergic kalafong ea mathata a lemalloang. Meriana ena e kenyelletsa acamprosate, N-acetylcysteine, D-cycloserine, gabapentin, lamotrigine, memantine, modafinil le topiramate. Hoa lokela ho hlokomeloa hore bongata ba meriana ena bo na le mekhoa ea ts'ebetso e kenyeletsang lits'ebetso tse ngata tsa methapo ea kutlo, mme mohlomong ntle le D-cycloserine, ha ho le e le 'ngoe e tsejoang ka sepheo sa ho lebisa phetiso ea glutamatergic kapa li-receptor tse khethehileng tsa glutamate. Leha ho le joalo, ho na le 'mele o matla oa bopaki ba pele ho nako bo hlahang lilemong tse fetang mashome a mabeli tsa lithuto tsa liphoofolo tse fanang ka maikutlo a karolo ea bohlokoa bakeng sa phetisetso ea glutamate le li-receptor tsa glutamate moputsong oa lithethefatsi, matlafatso le ho khutla hape (Nonyana le Lawrence, 2009; Bowers et al a., 2010; Gass le Olive, 2008; Kalivas et al a., 2009; Moussawi le Kalivas, 2010; Olive, 2009, 2010; Reissner le Kalivas, 2010; Tzschentke le Schmidt, 2003; Uys le LaLumiere, 2008). Bakeng sa kakaretso ea phetisetso ea glutamatergic le li-receptor tsa glutamate, 'mali o fetisetsoa tlhahlobisong ke Sanacora makasineng oa hajoale (mophatlalatsi - ka kopo kenya linomoro tse nepahetseng tsa maqephe mona). Ntle le moo, lingoliloeng tse nyane empa li ntse li hola ka ts'ebeliso ea meriana ena ho phekola bokhoba ba boits'oaro bo joalo ka papali ea papali ea chelete, le lithuto tse mabapi le taba ena le tsona li tla hlahlojoa.

2. Meriana ea Glutamatergic ea kalafo ea mathata a ts'ebeliso ea lithethefatsi

2.1. Acamprosate

2.1.1. Mokhoa oa Khato

Acamprosate (calcium acetylhomotaurine) e tsoa ho homotaurine, agonist e sa amaneng le γ-aminobutyric acid (GABA). Molek'hule e entsoe ka N-acetylated ho thusa ho kenella kahare ho tšitiso ea mali le bokong, mme e entsoe joalo ka letsoai la calcium ho eketsa ho kenella ha motsoako ho tsoa pampitšaneng ea meno. Leha e na le liphetoho tsena tsa lik'hemik'hale, bioavailability ea eona ka kakaretso e lula e le mpe (ke hore, <20%) mme e hloka litekanyetso ka bongata ba ligrama tse 2-3 ka letsatsi ho bonts'a katleho. Ho hlahisitsoe mekhoa e mengata ea litlhare tsa acamprosate, empa lithuto tsa pele tse bontšang hore acamprosate e etsa liketso tsa eona ka mekhoa ea glutamatergic e tlalehiloe ke Zeise le basebetsi-'moho le eena (Tseba et al a., 1990, 1993). Bafuputsi bana ba bonts'itse hore acamprosate e fokolitse nyakallo ea ho thunya ha neuronal ho hlahisitsoeng ke ts'ebeliso ea iontophoretic ea L-glutamate ho li-cortical neurons ho vivo, le ho sitisa menyetla ea postynaptic (EPSPs) e hlahisitsoeng ke glutamate le N-methyl-D-aspartate (NMDA). Bopaki bo bong bakeng sa ts'ebetso ea mohanyetsi oa NMDA ea ts'ebetso ea acamprosate bo tsoa liphuputsong tse bonts'ang hore motsoako ona o loants'a maqhubu a nyakallo a li-postynaptic (EPSCs) a NMDA ho li-hippocampal neurons (Rammes et al a., 2001le ho laola polelo ea subunit ea NMDA ka tsela e ts'oanang le e boneng kalafo e latelang le mohanyetsi oa NMDA ea sa hlolisaneng le MK-801 (Putzke et al a., 1996; Rammes et al a., 2001). Leha ho le joalo, bafuputsi ba bang ha ba fumane litlamorao tsa acamprosate phetisong ea synaptic e tsamaisanang le NMDA tikolohong ea CA1 ea hippocampus (Popp le Lovinger, 2000), Ha ba bang ba fumane hore acamprosate ehlile e ka etsa mosebetsi oa ho amohela li-NMDA sebakeng sa CA1 sa hippocampus (Madamba et al a., 1996) le li-nucleus accumbens (Berton et al a., 1998). Leha ho na le liphetho tse sa lumellaneng tsa electrophysiological, lithuto tse tlamang li netefalitse tšebelisano ea acamprosate le sebaka se tlamang sa spermidine-, glutamate- le / kapa MK-801 sa mamello ea NMDA (al Qatari et al a., 1998; Harris et al a., 2002; Naasila et al a., 1998), 'me ka hona acamprosate hangata e bitsoa ka mokhoa o sa tobang e le "modulator ea NMDA" (Setšoantšo sa 1). Leha lipehelo tse nepahetseng tsa limolek'hule tsa acamprosate li ntse li sa tiisoa ka tieo (Kiefer le Mann, 2010; Reile et al a., 2008), likhopolo-taba tsa morao-rao li hlahisa hore acamprosate e khutlisa ho se leka-lekane lipakeng tsa ts'isinyeho le thibelo ea amino acid neurotransmission e bakoang ke tšebeliso e mpe ea joala (MONGOLI OA TSOANG PELE: De Witte et al a., 2005; Kiefer le Mann, 2010; Spanagel et al a., 2005; Umhau et al a., 2010).

Setšoantšo sa 1 

Mekhoa ea ho kenya ts'ebetsong ea meriana ea 8 e khahlanong le lithethefatsi. Acamprosate - Sepheo sa limolek'hule sa acamprosate se ntse se sa tsitsa, empa lithuto tse 'maloa li bonts'itse e hlophisa tšebetso ea li-receptor tsa NMDA le ho khutlisa botsitso lipakeng ...

2.1.2. Katleho ea Kliniki

Pontšo ea pele ea ts'ebetso ea kliniki ea acamprosate ho fokotsa sekhahla sa ho khutlela mokhoeng oa joala e phatlalalitsoe bohareng ba bo-1980 (Lhuintre et al a., 1985). Ho theosa le lilemo, acamprosate e bonts'itse boholo ba litlamorao ho tloha ho tse nyane ho isa ho tse itekanetseng ho fokotsa ts'ebeliso ea joala ka botlalo, mehato e ikemetseng ea takatso ea joala, le ho khothaletsa ho ithiba, joalo ka ha ho hlahlobiloe litlhahlobong tsa morao-rao tsa meta (Kennedy et al a., 2010; Kiefer le Mann, 2010; Kranzler le Gage, 2008; monna et al a., 2008; Mason le Heyser, 2010a, b; Rosner et al a., 2010; Snyder le Bowers, 2008). Ka lebaka la ho fokola ha eona ka molomo, ho hlokahala litekanyo tse kholo tsa acamprosate (hangata ho 2-3 g ka letsatsi) ho bona ts'ebetso. Leha ho le joalo, phuputso e entsoeng haufinyane ea litsi tse ngata tsa bakuli ba fetang 1200 ba itšetlehileng ka joala (e tsejoang ka hore ke Meriana e Kopaneng le Litšebetso tsa Boitšoaro, kapa boithuto ba "COMBINE") e fumane hore acamprosate ha e sebetse ho feta placebo ho fokotsa sekhahla sa ho khutlela mokhoeng oa bongaka maemo a laoloang (Anton et al a., 2006). Liphuputso tse ling tsa morao-rao li bonts'itse ho haella ha acamprosate ho fokotsa tšebeliso ea joala kapa takatso, kapa ho khothaletsa ho ithiba (Donovan et al a., 2008; Laaksonen et al a., 2008; Morley et al a., 2006; Richardson et al a., 2008). Mabaka a liphuputso tsena tse mpe, haholo-holo ho latela liphuputso tse 'maloa tse fetileng (tse akaretsoeng litlhahlobong tse boletsoeng kaholimo), a ntse a phehisanoa khang. Bafuputsi ba bang ba hlahisitse hore "phello ea" placebo "ea bohlokoa thutong ea COMBINE e kanna eaba e patile litlamorao tsa acamprosate (Weiss et al a., 2008), le hore lintlafatso liphellong tse sa noeng tse amanang le maemo a joalo ka boleng ba bophelo li ne li hlile li le holimo ho bakuli ba tšoaroang ke acamprosate- khahlano le ba sebetsanang le placebo thutong ea COMBINE (LoCastro et al a., 2009). Ba bang ba khothalelitse hore ho qala kalafo ea acamprosate kamora ho tlosa 'mele ho hlahisa phokotso ea takatso ea joala ho fapana le ha e fanoa nakong ea ts'ebeliso e mpe ea joala (Kampman et al a., 2009), joalo ka ha ho entsoe thutong ea KOPANO. Tlhokahalo ea litekanyetso tse tharo ka letsatsi e kanna ea ba tšitiso ea ho latela bakuli ba bang. Ho fokotseha ha sepheo sa ho qala kalafo har'a ba tepelletseng maikutlo ha ho bapisoa le joala bo sa tepelletseng maikutlo ho ama haholo kalafo ea kalafo ho bakuli ba tšoaroang ke acamprosate (Lejoyeux le Lehert, 2011). Kamora nako, mabaka a mang a susumetsang joalo ka ho ba le sepheo sa kalafo sa ho ithiba ho fapana le ho noa ka mokhoa o itekanetseng a bonahala a na le litlamorao ho bakuli ba alafshoang ka acamprosate ha ba bapisoa le placebo (Mason et al a., 2006; Mason le Lehert, 2010). Ho ka etsahala hore, joalo ka kalafo efe kapa efe ea psychotropic, likaroloana tsa bakuli li ka arabela hantle ho acamprosate ho feta tse ling. Liphuputso tse ling li hlokahala ka kotloloho ho fumana hantle hore na ke eng lintho tsena tse khothatsang, mokhoa, sephetho, kapa mohlomong liphatsa tsa lefutso e le ho supa makhoba a tahi a nang le monyetla oa ho bontša karabelo e ntle ho acamprosate.

Mabapi le ts'ebeliso ea acamprosate ea ho phekola bokhoba ba lithethefatsi tse ling tsa tlhekefetso kapa litloaelo tsa boits'oaro joalo ka papali ea chelete, lithuto tse kholo ha li eo, mme lithuto tse 'maloa tse phatlalalitsoeng li tlalehile sephetho se fapaneng. Mohlala, tlaleho ea haufinyane ea linyeoe e tšehetse ts'ebeliso e ka bang teng ea acamprosate ho phekola papali ea chelete.Raj, 2010). Ka lehlakoreng le leng, Kampman le basebetsi-'moho le eena ba sa tsoa tlaleha hore tekong e laoloang habobebe e laoloang ke placebo ea bakuli ba 60 ba itšetlehileng ka "cocaine", acamprosate ha e bonts'a litlamorao ho ts'ebeliso ea cocaine, takatso kapa matšoao a ho tlohela ho bapisoa le bakuli ba fumanang placebo (Kampman et al a., 2011). Liphuputso tsena tsa morao-rao li nyahamisa haholo hobane liphuputso tse 'maloa tsa litoeba li bonts'itse hore acamprosate e thibela litlamorao tse ntle tsa koae hammoho le ts'ebeliso ea lithethefatsi le boits'oaro e khutliselitsoeng ea boits'oaro ba ho batla koae (Bowers et al a., 2007; Mcgeehan le Olive, 2003, 2006). Leha ho le joalo, ha ho fanoa ka boholo ba sampole le sekhahla se phahameng sa thuto se tsoang ke Kampman le basebetsi-'moho, monyetla o ntse o le teng oa hore acamprosate e ka ba molemo kalafong ea bokhoba ba k'hok'heine ka seteisheneng sa batho ba itšetlehileng ka k'hok'heine.

2.2. N-acetylcysteine ​​(NAC)

2.2.1. Mokhoa oa Khato

NAC ke sehlahisoa sa N-acetylated sa amino acid cysteine ​​ea tlhaho. Hang ha e se e le kahare ho litho tsa kahare tse kahare ho kenyelletsa le boko, NAC e fuoa deacetylated ho etsa cysteine ​​ea mahala, le homodimerization ea limolek'hule tse peli tsa cysteine ​​ka tlamo ea disulfide e baka sebopeho sa cystine. Kahoo, NAC e nkuoa e le cystine pro-drug e tlamang ho cystine-glutamate exchanger (eo hangata e bitsoang system xc-) mme e khothaletsa synthesis ea glutathione (Baker et al a., 2002; McBean, 2002). Ka metjhini ena NAC e ipakile e sebetsa hantle litleliniking joalo ka moemeli oa mucolytic le kalafong ea ho feta tekano ha acetaminophen. Leha ho le joalo, ntle le ho khothaletsa synthesis ea glutathione, system xc- ke protheine e khahlanong le thepa e fetisang cystine e kantle ho lisele ho lisele tsa glial le glutamate ea kahare ho tsoa ka hare ho glia ho ea tikolohong e kantle ho lisele. Phello e hlahisoang ke NAC ke ho phahama ha li-extracellular glutamate level, tse fokotsoang nakong ea ho tlohela k'hok'heine nako e telele (Baker et al a., 2002, 2003; Kau et al a., 2008; Madayag et al a., 2007; Melendez et al a., 2005; Moran et al a., 2005). "Tloaelo" ena ea li-extracellular glutamate level e khutlisetsa molumo oa glutamatergic ho presynaptic release-regulating group II metabotropic glutamate receptors (mGluR2 / 3, Moran et al a., 2005;; bona Setšoantšo sa 1) hape e thibela bokhoni ba phephetso ea "cocaine" e latelang ho eketsa maemo a "extracellular glutamate" ho "nucleus accumbens". Sephetho ke thibelo ea bokhoni ba ts'oaetso e matla ea cocaine ho khutlisa boits'oaro ba ho batla k'hok'heine (Amen et al a., 2011; Baker et al a., 2003; Kau et al a., 2008; Madayag et al a., 2007; Moran et al a., 2005; Moussawi et al a., 2009).

2.2.2. Katleho ea Kliniki

Ho ipapisitsoe le liphuputso tsena tsa lithuto tsa liphoofolo, ho sa tsoa phatlalatsoa lithuto tse 'maloa mabapi le katleho ea NAC ho fokotsa ts'ebeliso ea koae, takatso, matšoao a ho hula le ho khutlela morao ho batho ba lemaletseng koae. Phuputsong e nyane ea polokeho le mamello (n = lithuto tse 13), ho bonts'itsoe hore NAC (1200 mg / letsatsi matsatsi a mabeli) e mamelletsoe hantle ke ba lemaletseng koae mme e hlahisitse mekhoa e fokolang ea ho fokotsa litlaleho tsa bona tsa ts'ebeliso ea koae, ho lakatsa le matšoao a ho tlohela (LaRowe et al a., 2006). Liphuputso tse nyane tsa ho latela (n = Lihlooho tse 15-23) li netefalitse hore litekanyetso tse tšoanang tsa NAC li mamelloa hantle ke makhoba a k'hok'heine 'me ha e le hantle li hlahisa phokotso e kholo ts'ebelisong ea koae le ho lakatseng batho ba itšetlehileng ka kalafo ba batlang kalafo ea bakuli ba tlokotsing (Amen et al a., 2011; LaRowe et al a., 2007; Mardikian et al a., 2007). Habohlokoa, leha ho le joalo, phuputso ea haufinyane ea mofofisi e bontšitse hore NAC ha e fokolise maikutlo a ikhethang a "cocaine" e phahameng kapa "ho potlaka" kamora ho pepesetsoa video ea likarolo tse amanang le k'hok'heine, empa e fokotsa takatso e hlahisoang ke ts'oaetso e matla ea IV ea cocaine (Amen et al a., 2011). Le ha liphetho tsena tsa morao-rao li ka bonahala li sa lumellane le tsa LaRowe, Mardikian le basebetsi-'moho, ba fumaneng litlamorao tse fokotsang tsa NAC mabapi le takatso ea cue-evoke cocaine, mohlala o monyane haholo oa thuto ea Amen le basebetsi-'moho le eena (n = 4 lihlooho ) e ka fokotsa ho toloka ha eona. Ho sa tsotelehe, liphetho tsena tsa pele li fana ka tlhaiso-leseling e khothatsang eo NAC e ka bang ts'ebeliso e ka bang teng ho phekoleng bokhoba ba koae, 'me ho hlokahala liteko tse ling tsa litsi tsa kliniki tse ngata ho netefatsa liphetho tsena ka bongata.

Mabapi le lithethefatsi tse ling tsa tlhekefetso, teko e nyane ea morao-rao ea bongaka (n = lithuto tse 29) e fupulitse matla a NAC a ho thusa ho emisa ho tsuba (Mohlomphehi et al a., 2009). Liphetho tsa phuputso ena li bontšitse hore kalafo ea NAC (2400 mg / ka letsatsi) e fokotsa palo ea lisakerete tse tsubeloang ha ho bapisoa le lisakerete tse tsubuoang ke batho ba fumanang placebo, empa kalafo ea NAC ha ea ka ea fokotsa maemo a plasma carbon monoxide, matšoao a ho ntša nicotine, kapa nicotine Ho lakatsa. Phuputso e 'ngoe e nyane ea lifofane (n = lithuto tse 24) e bonts'itse hore NAC e fokotsa ts'ebeliso ea matekoane le ho lakatsa bacha ba holileng matekoane ba lilemo li 18 ho bapisoa le placebo (Gray et al a., 2010). Ha e le lithethefatsi tse seng tsa lithethefatsi, teko e nyane ea bongaka (n = lithuto tsa 23) e bonts'itse hore NAC (e bolelang tekanyetso e sebetsang ea 1477 mg / letsatsi) e theotse lintlha ho Yale Brown Obsessive Compulsive Scale Modified for Pathological Gambling [PG-YBOCS] (Grant et al a., 2007), 'me ho bonts'itsoe hore ho na le katleho ho fokotsa ho qobella ho loma lipekere ho amanang le lefu la ho ferekana kelellong ho bakuli ba bararo (Berk et al a., 2009). Kamora nako, NAC e boetse e bontšitsoe e hatella ho hula moriri ka boithuto bo habeli ba bakuli ba 50 ba nang le trichotillomania (Grant et al a., 2009).

Le ha lithuto tsohle tsa bongaka tse boletsoeng kaholimo e le tsa pele ebile li sebelisoa ka boholo bo boholo ba mehlala, litheko tse bonahalang li sa feto-fetohe tsa NAC li fana ka bopaki bo matla ba hore meriana ena, hammoho le metsoako e meng e khutlisetsang glutamate homeostasis (Mohlomphehi et al a., 2010; Sari et al a., 2009), e kanna ea ipaka e le lithuso tse sebetsang tsa kalafo ea kalafo ea kalafo ea lithethefatsi le boits'oaro.

2.3. D-cycloserine (DCS)

2.3.1. Mokhoa oa Khato

DCS (D-4-amino-3-isoxazolidone) ke sehlahisoa sa amine acid serine ea tlhaho. E sebetsa joaloka co-agonist setsing se tlamang glycine setulong sa NR1 sa mokelikeli oa NMDA, se teng ho li-receptor tsohle tsa NMDA tsamaisong ea methapo e bohareng. DCS ha ea lekana ho kenya li-receptors tsa NMDA ka botsona, 'me e hloka boteng ba tlamo ea glutamate ho amohelang moamoheli e le hore e hlahise litlamorao tsa eona. Ts'ebetso ea sebaka se tlamang glycine ke DCS e ntlafatsa ts'ebetso ea NMDA ka ho eketsa phallo ea calcium ka li-receptor tsena ntle le ho baka ts'oaetso ea methapo ea kutlo (Sheinin et al a., 2001;; bona Setšoantšo sa 1).

2.3.2. Katleho ea Kliniki

Ka lebaka la bokhoni ba eona ba ho ntlafatsa tšebetso ea li-receptor tsa NMDA, DCS ho lumeloa hore e tsamaisa polasetiki ea synaptic le mefuta e meng ea ho ithuta, ho kenyelletsa thuto ea boithuto ba Pavlovia le thuto ea ho fela, ka hona ho tlalehiloe hore e atlehile ho thusa ho felisoa ha likarabo tsa tšabo ka matšoenyeho. bakuli ba nang le bothata nakong ea kalafo ea ts'oaetso ea cue lithutong tse ngata tsa bongaka (e hlahlobisitsoe ho Davis et al a., 2006; Myers et al a., 2011; Myers le Davis, 2007). Mabapi le bokhoba, lithuto tsa liphoofolo li bonts'itse DCS e thusa ho felisoa ha sebaka se khethiloeng ke cocaine (CPP) (Botreau et al a., 2006; Thanos et al a., 2009), Ho fokotsa ho fumanoa bocha ha cocaine ho itaola ka ho ntlafatsa ho ithuta ho felang (Nic Dhonnchadha et al a., 2010), hape e thibela ho khutlisoa ha ts'ebetso ea k'hok'heine ka mokhoa o ikemetseng (Tlholohelo et al a., 2010). Leha ho le joalo, ke lithuto tse fokolang feela tsa kliniki tse mabapi le litlamorao tsa DCS mabapi le boits'oaro bo lemalloang tse seng li entsoe ho fihlela joale.

Santa Ana le basebetsi-'moho (Santa Ana et al a., 2009haufinyane e tlalehile hore ho batho ba tsubang lisakerete tse 12 tse itšetlehileng ka nicotine ba fumanang kalafo ea ts'oaetso, tsamaiso ea DCS (50 mg) e fokolitse haholo likarabo tsa mmele (ke hore, boitšoaro ba letlalo) hammoho le litekanyetso tsa maikutlo a ho tsuba ho arabela tlhahiso ea ho tsuba- lintlha tse amanang le tsona ha li bapisoa le lihlooho tse tšoaroang ke placebo (n = 13). Litaba tse tšoaroang ke DCS le tsona li bontšitse phokotso e felileng ea carbon monoxide maemong a tlhahlobo kamora beke e le 'ngoe, leha ho sa fumanoe litlamorao ho boits'oaro bo akaretsang ba ho tsuba. Liphuputso tsena tsa pele li fana ka maikutlo a hore DCS e ka ba molemo ho eketsa litlamorao tsa kalafo ea ts'oaetso nakong ea boiteko ba ho emisa ho tsuba koae. Ho fapana le moo, leha ho le joalo, phuputso e 'ngoe ea morao-rao e bontšitse hore lethal dose e tšoanang ea DCS e hlile e hlahisitse mokhoa oa ho eketseha ha litlaleho tse ikhethileng tsa takatso ea k'hok'heine ho batho ba 5 ba itšetlehileng ka cocaine (theko et al a., 2009). Nako ea tsamaiso ea DCS ho bakuli ba batlang kalafo e ka ba ea bohlokoa bakeng sa liphetho tsena tse bonahalang li sa lumellane. Mabapi le sena, ho bohlokoa ho hlokomela hore phuputso ea haufinyane ea liphoofolo e bonts'itse hore infusions ea DCS ho amygdala ea mantlha e hlile e ka matlafatsa ho kopantsoe ha mehopolo e amanang le cocaine likhopong tse itšebetsang tsa cocaine (lee et al a., 2009). Ho hlakile hore ho hlokahala lithuto tse ling ho lekola monyetla oa hore DCS e kanna ea ntlafatsa, ho fapana le ho thusa ho felisoa ha matla a ts'usumetso ea likhopolo tse amanang le cocaine. Ntle le moo, lithuto li hloka ho etsoa ho fumana hore na DCS e ntlafatsa katleho ea kalafo ea ts'oaetso ho batho ba lemaletseng lithethefatsi tse mpe ntle le k'hok'heine kapa nikotine, joalo ka lithuto tsa litlamorao tsa DCS ho batho ba seng lithethefatsi.

2.4. "Gabapentin"

2.4.1. Mokhoa oa Khato

Gabapentin ke moriana o thibelang likokoana-hloko o thibelang phetisetso ea methapo ea kutlo ka ho thibela matla a presynaptic voltage-gated Na+ le Ca2+ menyetla (Dickenson le Ghandehari, 2007; E ikhethang, 2007; Rogawski le Loscher, 2004). Ka lebaka leo, gabapentin e thibela ho lokolloa ha li-neurotransmitters tse fapaneng, ho kenyeletsoa le glutamate, joalo ka ha ho bontšitsoe ho Setšoantšo sa 1 (Coderre et al a., 2007; Cunningham et al a., 2004; Dooley et al a., 2000; Qoba et al a., 2000; Maneuf et al a., 2004; Maneuf le McKnight, 2001; Shimoyama et al a., 2000).

2.4.2. Katleho ea Kliniki

Liphuputso tse ngata li bonts'itse hore gabapentin e sebetsa hantle ho fokotsa matšoao a sa tloaelehang a ho tlohela joala (Bonnet et al a., 1999; Bozikas et al a., 2002; Mariani et al a., 2006; Martinez-Raga et al a., 2004; Myrick et al a., 1998; Rustembegovic et al a., 2004; Voris et al a., 2003), e atisang ho hlahisa CNS hyperexcitability le ho tsitsipana. Gabapentin e boetse e bontšitsoe e phahametse benzodiazepine lorazepam ho fokotsa litšitiso tsa boroko tse amanang le ho tlohela joala (Malcolm et al a., 2007). Ho fihlela joale, lithuto tsa bongaka mabapi le matla a kalafo ea gabapentin ho fokotsa ts'ebeliso ea lithethefatsi, takatso kapa ho khutlela morao li hlahisitse litholoana tse fapaneng. Liphuputso tse 'maloa li bontšitse hore gabapentin (e nang le litekanyetso tsa litekanyetso tsa 600-1200 mg / ka letsatsi) ha e fokolise ts'ebeliso ea k'hok'heine ho batho ba lemaletseng lithethefatsi (Bisaga et al a., 2006; Gonzalez et al a., 2007), Ha lithuto tse ling li bonts'a hore gabapentin ehlile e fokotsa ts'ebeliso e matla ea cocaine le takatso (Berger et al a., 2005; Myrick et al a., 2001; Raby, 2000; Raby le Coomaraswamy, 2004), mohlomong ka ho fokotsa litlamorao tsa ts'usumetso ea k'hok'heine (Haney et al a., 2005). Liphuputso tsa morao-rao li bonts'itse hore gabapentin (600-1500 mg / ka letsatsi) e fokotsa takatso le tšebeliso ea joala (Furieri le Nakamura-Palacios, 2007; Mason et al a., 2009; Myrick et al a., 2009), hape e lelefatsa nako ea ho ithiba ho noeng lino tse tahang (Broker et al a., 2008). Leha ho le joalo, bafuputsi ba bang ha ba bonts'a litlamorao tsa litekanyetso tse tšoanang tsa gabapentin takatsong ea joala (Bisaga le Evans, 2006; Myrick et al a., 2007). Ntle le moo, ho tlalehiloe hore gabapentin ha e fokotse tšebeliso ea methamphetamine (Heinzerling et al a., 2006), E na le litlamorao tse fokolang ho nts'etsapele ho ithiba ho tsubeng (White et al a., 2005), 'Me ha e ntlafatse matšoao a ho ikhula a ikhethileng lithutong tse itšetlehileng ka opiate (Kheirabadi et al a., 2008). Ha li kopantsoe hammoho, tlhaiso-leseling ena e bontša hore gabapentin e sebetsa hantle bakeng sa kalafo ea matšoao a ho tlohela joala mme e ka ba le katleho e itseng bakeng sa ho fokotsa takatso ea joala kapa k'hok'heine (leha e se lithuto tsohle tse tšehetsang mohopolo ona), empa meriana ena ha e na monyetla oa ho ho fokotsa ho lemalla lisakerete, methamphetamine, kapa ho fokotsa matšoao a ho khaotsa ho tsuba. Ho tsebo ea rona, gabapentin ha e e-so hlahlojoe hore na e sebetsa hantle hakae kalafong ea litlolo tsa boitšoaro.

2.5. Lamotrigine

2.5.1. Mokhoa oa Khato

E ts'oanang le gabapentin, lagotrimine ke anticonvulsant e thibelang presynaptic voltage-gated Na+ le Ca2+ menyetla (Dickenson le Ghandehari, 2007; E ikhethang, 2007; Rogawski le Loscher, 2004), ka hona e thibela ho lokolloa ha li-neurotransmitters tse fapaneng, ho kenyeletsoa le glutamate (bona Setšoantšo sa 1; Ahmad et al a., 2004; Cunningham le Jones, 2000; Leach et al a., 1986; Lees le Leach, 1993; Lingamaneni le Hemmings, 1999; Sitges et al a., 2007; Theoh et al a., 1995; Waldmeier et al a., 1995, 1996; Wang et al a., 2001). Lamotrigine e na le kotsi e sa tloaelehang empa e le kotsi ea ho baka lekhopho le matla la letlalo, le tsejoang ka lebitso la Stevens-Johnson Syndrome. Kotsi ea ho hlaha ha litla-morao tsena e ka theoloa haholo ke ho theola litekanyetso butle-butle, hangata ho qala ka lethal dose la 25 mg / ka letsatsi le ho theola beke le beke ho ea tekanyong ea 200-300 mg / ka letsatsi.

2.5.2. Katleho ea Kliniki

Joalo ka gabapentin, lamotrigine e thibela matšoao a somatic a ho tlohela joala (Krupitsky et al a., 2007b). Liphuputso tsa morao-rao tsa bongaka li bontša hore lamotrigine e boetse e bonahala e sebetsa hantle ho fokotsa takatso le tšebeliso ea k'hok'heine (Berger et al a., 2005; Brown et al a., 2003, 2006; Margolin et al a., 1998; Pavlovic, 2011), leha e bonahala e siea litlamorao tsa "cocaine" li sa fetoha (Mariha et al a., 2000). Liphello tse tšoanang tse fokotsang tsa lamotrigine mabapi le takatso ea joala (Rubio et al a., 2006inhalants)Shen, 2006) li tlalehiloe. Liphuputso tsena li fana ka maikutlo a hore lamotrigine e ka ba molemong oa bongaka kalafong ea bokhoba ba ts'ebeliso ea k'hok'heine, joala kapa lithethefatsi tse hlekefetsoang. Liphuputso mabapi le katleho ea lamotrigine kalafong ea litlolo tsa boitšoaro kapa lithethefatsi ho li-opiate, nicotine, kapa li-psychostimulants tse kang methamphetamine lia haella.

2.6. Memantine

2.6.1. Mokhoa oa Khato

Memantine ke mohanyetsi ea se nang tlholisano ho amohelang NMDA (Setšoantšo sa 1) mme e sebelisoa haholo bakeng sa kalafo ea ts'oaetso ea ts'oaetso ea lefu la Alzheimer's. Ntle le liketso tsa eona tsa bahanyetsi ho li-receptors tsa NMDA, memantine e boetse e thibela mofuta oa serotonin mofuta oa 3 receptor (5-HT3hammoho le nicotinic acetylcholine receptors. Le ha lintho tse ling tsa tlhekefetso joalo ka phencyclidine, ketamine, dextromethorphan kapa joala li na le thepa ea mohanyetsi ho amohelang NMDA, memantine ke e 'ngoe ea bahanyetsi ba seng bakae ba li-receptor tsa NMDA tseo hangata li mamelloang ke batho ebile ho sa bonahale li na le monyetla oa tlhekefetso (Vosburg et al a., 2005).

2.6.2. Katleho ea Kliniki

Ntle le ho sebetsa hantle ho fokotsa matšoao a ho khaotsa ho tlohela joala (Krupitsky et al a., 2007b) le bokhoba ba opiate (Bisaga et al a., 2001), memantine (tekanyetso e tloaelehileng ea 30-60 mg / day range) ho tlalehiloe e phahametse placebo ho fokotsa ho noa le / kapa ho lakatsa joala lithutong tsa joala (Arias et al a., 2007; Bisaga le Evans, 2004; Krupitsky et al a., 2007a). Kholiso ena ea takatso ea joala e kanna ea ba litholoana tsa litlamorao tse tšoanang le joala tsa memantine (Bisaga le Evans, 2004; Krupitsky et al a., 2007a). Leha ho le joalo, phuputso e khōloanyane e laoloang ke "placebo" e bontšitse hore memantine ha e fokotse boitšoaro bo nooang bo sa khaotseng ba bakuli ba itšetlehileng ka joala (Evans et al a., 2007). Memantine e tlalehiloe e fokotsa litlamorao tsa ho tsuba koae (Jackson et al a., 2009le heroine e kenang methapong (Ho tla le Sullivan, 2007); Leha ho le joalo, haholo-holo litekanyetsong tse phahameng, memantine e ka eketsa litlamorao tse ikhethang le tsa pelo le methapo ea cocaine (Collins et al a., 1998, 2007). Ka kakaretso, lintlha tsena li fana ka maikutlo a hore memantine e ka ba ts'ebeliso e ka bang teng ts'ebetsong ea bakuli ba ts'epahalang ba joala kapa joala, mme mohlomong e le sehlahisoa sa kalafo sa tahi. Leha ho le joalo, matla a eona a ho phekola bokhoba ba lithethefatsi tse ling tsa tlhekefetso a ntse a sa tsejoe, mme ho bonahala eka ho ka hanyetsoa bakeng sa ho phekola bokhoba ba k'hok'heine. Leha ho le joalo, phuputso e entsoeng haufinyane ea lifofane e bontšitse hore memantine e theotse lintlha tsa PG-YBOCS le nako e sebelisitsoeng ho becha ho batho ba 29 ba papali ea chelete.Grant et al a., 2010b), Ho fana ka maikutlo a hore memantine e ka ba ts'ebeliso e ka bang teng kalafong ea litlolo tse mpe tse kang papali ea chelete.

2.7. Modafinil

2.7.1. Mokhoa oa Khato

Modafinil ke tšusumetso ea CNS eo qalong e neng e etselitsoe ho matlafatsa ho tsoha le ho fadimeha kalafong ea boroko le boroko bo feteletseng ba mots'eare bo bakoang ke ho koaleha moea ka nakoana borokong kapa ho fetoha. Ka linako tse ling Modafinil e laeloa e le kalafo e sa sebetseng bakeng sa bothata ba ho se tsotelle / ho se sebetse hantle. Le ha mekhoa ea eona ea ts'ebetso ea neuropharmacological e e-so utloisisoe ka botlalo, modafinil ha e bonahale e sebetsa joalo ka mokelikeli oa monoamine joalo ka ha ho le joalo ka lintho tse matlafatsang tse kang amphetamine. Ho e-na le hoo, modafinil e ka sebetsa ka ho hlohlelletsa α-adrenoceptors, ho hatella GABA ho lokolloa, ho thibela mohatelli oa dopamine hampe, kapa ho susumetsa li-neurone tse nang le orexin tse nang le hypothalamic (Ballon le Feifel, 2006; Martinez-Raga et al a., 2008). Mekhoa e meng ea ts'ebetso e tlalehiloeng e kenyelletsa phokotso ea ho tsamaisa li-radicals tsa mahala le cytotoxicity e bakoang ke ho hloka boroko (Gerrard le Malcolm, 2007). Le ha lipatlisiso tse ngata li fana ka maikutlo a hore dopaminergic e na le litlamorao tse matlafatsang (Andersen et al a., 2010; Volkow et al a., 2009; Wisor le Eriksson, 2005), modafinil e bonts'itsoe ho phahamisa maemo a kantle ho lisele tsa glutamate libakeng tse ngata tsa boko ho kenyelletsa le dorsal striatum, hippocampus le diencephalon (bona Setšoantšo sa 1) (Ferraro et al a., 1997, 1998, 1999Ntle le ho ama synthesis ea glutamate (Perez de la Mora et al a., 1999). Modafinil e nkuoa e na le monyetla o tlase oa tlhekefetso (Martinez-Raga et al a., 2008), leha litlaleho tsa tlhekefetso li ka ba teng ka bongata bo phahameng (Andersen et al a., 2010Ts'ebeliso e seng ea bongaka ea eketseha (Ballon le Feifel, 2006). Ka lebaka leo modafinil hajoale o khethiloe e le ntho e laoloang ea Lenaneo la IV ke Tsamaiso ea Ts'ebetsong ea Lithethefatsi. Tekanyo e sebetsang ea bongaka ea modafinil hangata e maemong a 200-400 mg / letsatsi.

2.7.2. Katleho ea Kliniki

Litlaleho tse ngata tsa bongaka li bontšitse hore modafinil e bonts'a bokhoni ba ho phekola bokhoba ba koae (Martinez-Raga et al a., 2008). Phuputsong e nyane e laoloang ea tšebelisano-'moho ea lithethefatsi le Dackis le basebetsi-'moho le eena, ho tlalehiloe hore modafinil (200 mg / ka letsatsi) o sentse litlamorao tsa thabo ea koae e kenang methapong ea batho ba lemaletseng koae (Dackis et al a., 2003), 'me liphuputso tsena li ile tsa phetoa hamorao ka boikemelo (Malcolm et al a., 2006). Phuputso e laoloang habobebe e laoloang ka "placebo" ea bakuli ba batlang kalafo ba tlokotsing e bontšitse hore modafinil (400 mg / letsatsi) e fokolitse ts'ebeliso ea koae ea letsatsi le letsatsi le ho ithiba nako e telele (Dackis et al a., 2005). Teko ea morao-rao ea litsi tsa bophelo bo botle e fumane hore modafinil e fokotse ts'ebeliso ea k'hok'heine le takatso ho batho ba itšetlehileng ka cocaine ntle le ts'ebeliso e mpe ea joala (Anderson et al a., 2009). Le ha tlhaiso-leseling ena e bontša hore modafinil e kanna ea sebelisoa kalafong ea bokhoba ba k'hok'heine, ho ka etsahala hore tse ling tsa litlamorao li ka ba teng ka lebaka la ho fokotseha ha palo e phahameng ea mali a cocaine ka har'a modafinil (Donovan et al a., 2005). Modafinil e boetse e hlahisitse mekhoa e sa reng letho ho fokotseha ts'ebelisong e sebetsang ea methamphetamine har'a batho ba sebelisang hampe sethethefatsi sena (Shearer et al a., 2009), le phokotso ea boitšoaro ba papali ea chelete ho batho ba nang le bothata ba papali ea chelete (Zack le Poulos, 2009). Leha liphetho tsena tse ntle li supa monyetla oa ho ba modafinil ea ho phekola bokhoba ba psychostimulant le batho ba bapalang papali ea chelete, phuputso ea haufinyane e bonts'itse hore modafinil ha e na thuso ho fokotsa ho tsuba koae mme e hlile e hlahisa matšoao a mangata a ho tlohela le ho ameha hampe ho feta ho batho ba tsubang ba nang le placebo (Schnoll et al a., 2008). Kahoo, modafinil ha e bonahale e loketse ho sebelisoa kalafong ea ho khaotsa ho tsuba.

Ho latela pono ea methapo ea kutlo, ho batla ho ferekanya hore na hobaneng sethethefatsi se kang modafinil, se eketsang maemo a kantle ho lisele tsa glutamate, se baka phokotso ea tšebeliso ea k'hok'heine, ka lebaka la lithuto tse ngata tsa liphoofolo li bontšitse hore thibelo ea neurotransmission ea glutamatergic (ke hore, ka tsamaiso ea ionotropic Bahanyetsi ba amohelang li-glutamate, bahanyetsi ba li-postynaptic mGluR, kapa li-agonists tsa presynaptic mGluR2 / 3 tse hatellang ho lokolloa ha glutamate) li fokotsa matlafatso ea cocaine le / kapa ho khutlisetsa boits'oaro ba ho batla koae (Gass le Olive, 2008; Kalivas et al a., 2009; Knackstedt le Kalivas, 2009; Olive, 2009; Tzschentke le Schmidt, 2003). Khopolo-taba e 'ngoe e ka bang teng bakeng sa mokhoa oa ho etsa modafinil ho fokotsa takatso ea k'hok'heine ke ka ho fokotsa phokotso ea li-glutamate tse kantle ho lisele tse bonoang khubung ea li-accumbens nakong ea ho tlosoa ha cocaine, le ho fokotsa bokhoni ba likhokahano tsa cocaine kapa tse amanang le cocaine ho tsosa takatso (e ts'oanang le mokhoa oa ts'ebetso oa NAC - Setšoantšo sa 1). Lithuto tse ling li hlokahala ho leka khopolo-taba ena.

2.8. Topiramate

2.8.1. Mokhoa oa Khato

Topiramate, joalo ka li-anticonvulsants tse ling tse kenyeletsang gabapentin le lamotrigine, e na le mekhoa e mengata ea ts'ebetso, ho kenyeletsoa thibelo ea presynaptic voltage-gated Na+ le Ca2+ liteishene (ka tsela eo li thibela ho lokolloa ha li-neurotransmitters ho kenyelletsa glutamate) le ts'ebetso ea mofuta oa A GABA (GABA)Ali-receptor (Dickenson le Ghandehari, 2007; E ikhethang, 2007; Rogawski le Loscher, 2004). Ntle le moo, ho sa tsoa bontšoa ha topiramate hape e le mohanyetsi ho li-receptors tsa α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) e nang le subluit ea GluR5 (Setšoantšo sa 1) (Gryder le Rogawski, 2003; Kaminski et al a., 2004). Liketso tsena tsa ts'ebetso ea AMPA receptor li na le thahasello e khethehileng ho tloha ha mofuta ona oa glutamate receptor subtype o bontšitsoe haholo liphetohong tsa neuroadaptive tse hlahisoang ke lithethefatsi tsa tlhekefetso ekasitana le ho kena lipakeng ho itaola ha lithethefatsi le boits'oaro bo tšoanang le ba bona (Bowers et al a., 2010; Gass le Olive, 2008; Niehaus et al a., 2009; Xi le Gardner, 2008). Mefuta e tloaelehileng ea "topiramate" e tsoang ho 75-350 mg / ka letsatsi.

2.8.2. Katleho ea Kliniki

Ntle le ho fokotsa matšoao a ho tlohela joala a ts'oanang le a bonoang ke gabapentin le lamotrigine (Krupitsky et al a., 2007b), topiramate e kanna ea thusa ho ntlafatseng matšoao a benzodiazepine a ho hula (Michopoulos et al a., 2006). liphuputso tse ngata li phatlalalitsoe lilemong tse leshome tse fetileng tse bonts'ang katleho ea topiramate ho fokotsa litlamorao tsa joala, takatso ea joala le tšebeliso e matla ea bakuli ba tahang (Anderson le Oliver, 2003; Johnson et al a., 2004; Kenna et al a., 2009; Komanduri, 2003; Ma et al a., 2006; Miranda et al a., 2008; Rubio et al a., 2004). Bokhoni ba topiramate ea ho fokotsa ho noa ho tlōla bo ka bakoa ke bokhoni ba eona ba ho ferekanya maikutlo le ho ntlafatsa boits'oaro ba boits'oaro (Rubio et al a., 2009). Phuputso e 'ngoe e bile ea fumana lits'oants'o tsa hore topiramate e ne e phahametse meriana ea "standard standard ea khauta" e khahlanong le tahi naltrexone ho lelefatsa ho itlopa joala le ho fokotsa ho noa le ho tsuba hape (Baltieri et al a., 2008). Kahoo, topiramate e bonahala e le moriana o tšepisang ho sebelisoa kalafong ea botahoa.

Mabapi le lithethefatsi tse ling tsa tlhekefetso, topiramate e bontšitsoe e fokotsa tšebeliso ea koae le takatso ea batho ba itšetlehileng ka cocaine (Kampman et al a., 2004; Reis et al a., 2008), empa boholo ba mehlala e nyane ea lithuto tsena tse peli tsa kliniki li na le moeli (Minozzi et al a., 2008). Tlaleho ea nyeoe e bontšitse hore topiramate e fokotsa ts'ebeliso ea methylenedioxymethamphetaine (MDMA, "Ecstasy") (Akhondzadeh le Hampa, 2005). Ho batho ba tsubang sakerete, lithuto tse ling tse nyane li bonts'itse litlamorao tse ntle tsa topiramate ho khothaletsa ho ithiba ho tsuba kapa ho fokotsa boits'oaro ba ho tsuba (Arbaizar et al a., 2008; Johnson et al a., 2005; Khazaal et al a., 2006). Bokhoni ba topiramate ba ho lelekela ho tsuba e ka ba bo ikhethileng ka bong, ka likarabo tse ntle ho banna (Anthenelli et al a., 2008). Leha ho le joalo, phuputso e 'ngoe e fumane hore, joalo ka lamotrigine, topiramate e ekelitse litlamorao tsa ho tlohela ho tsuba hammoho le litlamorao tsa sakerete e tsubang mme ha e a ka ea ama takatso e bakoang ke takatso (Reid et al a., 2007), Ho belaella ts'ebeliso e ka bang teng ea topiramate e le thuso ea ho emisa ho tsuba. Ka mokhoa o ts'oanang, topiramate e bontšitsoe ho ntlafatsa maikutlo a matle a hlahisoang ke methamphetamine (Johnson et al a., 2007). Kahoo, topiramate e kanna ea ba le ts'episo ea ho thusa kalafong ea tahi le joala mohlomong le cocaine le nikotine, empa lithuto tse ling lia hlokahala ho lekola bokhoni ba eona e le kalafo ea ho phekola bokhoba ba lithethefatsi tse ling tsa tlhekefetso.

Mabapi le ho lemalla boitšoaro, lithuto tse nyane le litlaleho tsa linyeoe li phatlalalitsoe lilemong tsa morao tjena tse bontšang hore topiramate le eona e ka sebelisoa ho phekoleng mathata ana. Ho fihla hajoale, litlamorao tse ntle tsa topiramate li bonoe ho fokotsa ho khutlela bothateng ba ho becha ()Dannon et al a., 2007) le ho fokotsa ho ja ka mokhoa o qobelloang le boitšoaro ba thobalano (Fong et al a., 2005; Khazaal le Zullino, 2006; Tata le Kockler, 2006). Ho hlakile hore mokhoa ona oa kalafo ea lithethefatsi tse seng lithethefatsi o lokela ho hlahlojoa ho ea pele.

3. Kakaretso le sephetho

Mabapi le meriana e robeli e hlahlojoang mona e nang le ts'ebetso ea ts'ebetso ea glutamatergic (acamprosate, NAC, DCS, gabapentin, lamotrigine, memantine, modafinil, le topiramate), re fihlela qeto ea hore NAC, modafinil, le topiramate li ngotsoe hantle ebile monyetla o moholohali oa ho sebelisoa kalafong ea litlhare tsa lithethefatsi le boits'oaro. Ehlile meriana efe kapa efe e hlahlojoang mona e ke ke ea e-ba pheko bakeng sa lithethefatsi tsohle, empa e kanna ea ba thuso e sebetsang ea kalafo ea meriana ho kalafo e tloaelehileng ea kelello kapa kalafo ea boits'oaro ea ho phekola bokhoba ba lithethefatsi tse ling tsa tlhekefetso (haholo k'hok'heine le joala) hammoho le lithethefatsi tse seng lithethefatsi (haholo-holo papali ea chelete). E kopantsoe le liteko tse tloaelehileng tsa morao-rao kapa sephetho se lekantsoeng sa ho khetholla mefuta e meng ea batho ba lemaletseng lithethefatsi e ka arabelang hantle meriana e le 'ngoe kapa e meng, ka litla-morao tse fokolang haholo, mehla ea kamora' genomic ea ts'epo e tla lumella bafuputsi le lingaka ho sebelisa meriana ea meriana mekhoa ea ho khetholla bao e ka bang ba arabelang le bao e seng ba arabelang e 'ngoe le e' ngoe ea meriana ena pele ba qala kalafo. Palo e lekanyelitsoeng ea data e fumanehang bakeng sa tse ling tsa metsoako ena, joalo ka DCS le lamotrigine, e fana ka tumello ea lithuto tse kholo tsa litsi tse ngata. Ntle le moo, lipatlisiso tse eketsehileng ka mefuta e loketseng ea liphoofolo ka mekhoa e nepahetseng ea glutamatergic e hokahanyang likarolo tse fapaneng tsa potoloho ea bokhoba ba tahi (ke hore, ts'ebeliso e mpe ea lithethefatsi, ho tlohela, ho lakatsa, boits'oaro ba ho batla lithethefatsi, le ho oela hape) ka ts'epo ho tla lebisa ho mekhoa e atlehang ea litlhare eo e ka sebelisoa ho kenella maemong a itseng a tahi.

Liteboho

Bangoli ba rata ho leboha Katie Ris-Vicari ka thuso ea hae mabapi le ho hlahisa litšoantšo. Mosebetsi ona o ne o tšehelitsoe ke lithuso tsa NIH DA024355, DA025606, le AA013852 (MFO).

Mongolo o botlaaseng ba leqephe

Boitlhotlhollo ba Mohoeletsi: Ena ke faele ea PDF ea mongolo o ngotsoeng ka letsoho o sa amoheloang o amoheletsoeng bakeng sa ho hatisoa. Joaloka tšebeletso ho bareki ba rona re fana ka phetolelo ena ea pele ea mongolo o ngotsoeng ka letsoho. Mongolo o ngotsoeng ka letsoho o tla ba le ho kopitsa, ho kenya lihlopha le ho hlahloba bopaki bo hlahang pele o hatisoa ka mokhoa oa oona oa ho qetela. Ka kopo hlokomela hore nakong ea mekhoa ea tlhahiso ea lihlahisoa e ka fumanoa e ka amang litaba, le litsebiso tsohle tsa molao tse sebetsang koranteng e amanang le eona.

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