- Biomed Res Int. 2014; 2014: 109786.
- E hatisitsoe Inthaneteng 2014 Jun 12. doi: 10.1155/2014/109786
PMCID: PMC4075088
Mauro Pettorruso, 1,* Luisa De Risio, 1 Giovanni Martinotti, 2 Marco Di Nicola, 1 Filippo Ruggeri, 1 Gianluigi Conte, 1 Massimo di Giannantonio, 2 'me Luigi Janiri 1
Sehlooho sena se bile teng e boletsoeng ke lihlooho tse ling ho PMC.
inahaneloang
Bothata ba ho becha kapa ho becha ho hlalositsoe ke DSM-5 e le tšibollo ea boitšoaro. Ho fihla joale, pathophysiology ea eona ha e utloisisoe ka botlalo mme ha ho na kalafo e amoheloang ke FDA bakeng sa mathata a papali ea chelete. Glutamate ke "neurotransmitter" e ka sehloohong tsamaisong ea methapo, 'me haufinyane e kentse letsoho ho pathophysiology ea boits'oaro bo bobebe. Tokomaneng ena, re lekola lingoliloeng tsa hajoale sehlopheng sa lithethefatsi tse sebetsang e le mokhoa oa ho tsamaisa glutamate system ho PG. Palo ea lithuto tse 19 li kenyellelitsoe ho latela mekhoa ea ho kenyelletsoa le ho khetholloa. Teko ea bongaka le letoto la linyeoe tse sebelisang lithethefatsi tsa glutamatergic (N-acetylcysteine, memantine, amantadine, topiramate, acamprosate, baclofen, gabapentin, pregabalin, le modafinil) li tla hlahisoa ho hlakisa katleho ea boits'oaro ba papali ea chelete le litekatsong tse amanang le tleliniki (ho lakatsa, ho tlohela. , le matšoao a kelello) ho bakuli ba PG. Liphetho li 'nile tsa tšohloa ho fumana leseli le eketsehileng ho pathophysiology le kalafo ea PG. Ka ho phethela, ho qhekella ha glutamatergic neurotransication ho bonahala ho ts'episa ho nts'etsapele basebeletsi ba ntlafatsang ba kalafo bakeng sa kalafo ea mathata a ho becha. Ho hlokahala lithuto tse ling hape. Kamora nako, re hlahisa litlhahiso le mathata a kamoso sebakeng sena sa lipatlisiso.
1. Semelo
Ho becha ka tsela ea tlhaho (PG) ho bontšoa ka boitšoaro bo phehellang le bo bobe ba ho becha, moo batho ka bomong ba kenang mekheng ea ho becha khafetsa le ha ho na le litlamorao tse mpe [1]. Boloetse ba papali ea chelete bo ama 0.2-5.3% ea batho ba baholo lefatšeng ka bophara; litlamorao tse bohloko tsa pherekano ena ea boits'oaro hangata li baka tšenyo e kholo maphelong a bakuli le ba malapa a bona. Ho fihla joale, ha ho na kalafo e lumelletsoeng ke FDA bakeng sa PG, leha ho na le lilemo tse ka bang leshome tse entsoeng patlisiso e matla, le maano a sebetsang a kalafo a lula e le phephetso. Haufinyane, PG e kentsoe sehlopheng sa tlhahlobo ea tšebeliso ea lithethefatsi le mafu a tlhekefetso khatisong ea 5 ea Diagnostic and Statistical Manual of Mental Dis shida (DSM-V).
Glutamate (Glu) ke "neurotransmitter" e ka sehloohong tsamaisong ea methapo. Ho sa tsoa etsoa tlhahiso ea hore ts'ebeliso ea lithethefatsi e ka bonoa e le lebaka la bokhoni bo sitisang ho thibela lithethefatsi ho latela maemo a tikoloho, ka lebaka la liphetoho tse tlisoang ke Glu homeostasis, hammoho le ts'ebetso e kopaneng ea sensopised dopamine (DA) le N-methyl-d- aspartate (NMDA) li-glutamatergic receptors [2]. Ho thibela tokollo ea Glu ho thibetse boitšoaro ba ho batla lithethefatsi ho liphoofolo le bakuli ba nang le mathata a tšebeliso ea lithethefatsi [3, 4]. Ho tšoana le tsa likokoana-hloko lipakeng tsa PG le bokhoba ba lithethefatsi [5] fana ka tlhahiso ea hore bakuli ba PG ba ka rua molemo ho lingaka tse sebelisetsoang ho phekola bokhoba ba lithethefatsi le hore mehlala ea pathophysiological ea ho lemalla lithethefatsi e ka ba bohlokoa ho PG le eona.
Ka pampiri ena, re lekola lingoliloeng tsa hajoale ka lithethefatsi tse fetolang glutamatergic neurotransication ho PG. Re boetse re hlakisa li-hypotheses tsa hona joale ho neurobiology ea PG, re tsepamisa maikutlo ho li-neurotransmission tsa glutamatergic le tšebelisano ea eona le li-neurotransmitters tse ling. Liteko tsa kliniki le letoto la linyeoe tse sebelisang lithethefatsi tsa glutamatergic li tla hlahisoa ho hlakisa katleho ea boits'oaro ba papali ea chelete le likarolo tse ling tsa kliniki tse amanang le eona (ho lakatsa, ho tlohela, le matšoao a kelello) ho bakuli ba PG. Liphetho li tla tšohloa ho fumana leseli le fetang la pathophysiology le kalafo ea PG. Kamora nako, re hlahisa litlhahiso le mathata a kamoso sebakeng sena sa lipatlisiso.
2. Mekhoa
Bahlahlobisisi ba babeli ba ne ba kentse letsoho tlhahlobo ena kamora ho ts'oaroa ha mokhoa o le mong oa phuputso ea libuka le litekanyetso. Patlo ea Libibele e ne e le tlhahlobo ea likhomphutha tsa database tsa Medline, Scopus, le Google Scholar ka Pherekhong 2014. Ho ile ha hlahlojoa lithuto tsa puo ea Senyesemane feela lilemong tse leshome tse fetileng. Re sebelisitse lipotso tse latelang: "gambl *" e kopantsoe le "glutamate" le lethathamo la li-ejotransication-modulating agents tse kopantsoeng le N-acetylcysteine, memantine, amantadine, acamprosate, topiramate, lamotrigine, baclofen, gabapentin, pregabalin, modafinil dizocilpine, LY354740, D-cycloserine, methadone, le dextromethorphan. Lipatlisiso li hlahisitse litholoana tse 99 qalong. Ka mor'a moo re ne re batla lipatlisiso tse amanang le sehlooho se seng le se seng ho kenyeletsa le lithuto tsa pejana ka sehlooho seo.
Ho lingoloa tse 99 tse ka bang teng, tse 19 li kenyelelitsoe (Setšoantšo sa 1) ho latela maemo a latelang: (a) bothata bo hlahileng ke PG; (b) ho sa feleng ho teng; (c) phatlalatso ke pampiri ea pele, ntle le litekolo; (d) thuto ke patlisiso ea neurobiological kapa ea bongaka lithutong tsa PG.
Lethathamo 1 e bonts'a data e amehang ho tsoa lingoloa tse kenyellelitsoeng thutong: lithethefatsi tse sebelisitsoeng, litekanyetso, moralo oa lipatlisiso, boholo ba sampole le palo ea batho ba shebiloeng, mekhoa, sephetho sa temohisiso, le sepheo se ka sehloohong sephethong sa papali ea chelete.
3. Phetisetso ea Glutamatergic ho li-Behaviors tse Tlatsetsang: Bohlokoa ba Papali ea Pathological
Glu ke eona neurotransmitter e atileng ka ho fetesisa ho CNS mme ketso ea eona e laoloa ke mefuta e 'meli ea li-receptors: li-receptors tsa ionotropic (iGlu) le metabotropic (mGlu). Li-receptor tsa ionotropic ke liteishene tsa ion tseo, ha li kopana le Glu, li eketsang bongata ba methapo ea sodium le potasiamo e bakang ho putlama ha membrane [19]. Li arotsoe ka li-subtypes tse tharo: N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoazole-propionic acid (AMPA), le kainate. Li-receptor tsa metabotropic ke li-receptor tsa G protein-coupled 'me li arotsoe ka lihlopha tse tharo (I, II, le III) ho latela ts'ebetso ea Homology ea tatellano, mochine oa phetisetso ea matšoao, le khetho ea bona ea pharmacological [20]. Li-receptor tsa metabotropic li fumaneha haholo libakeng tse nang le maoto le matsoho a ka pele, a amehang ka ho khetheha mokhoeng oa ho lemalla. Haholo-holo, li-receptors tsa sehlopha ho bonahala ke na le karolo ea bohlokoa ho taolo ea litlamorao tse matlafatsang tsa lithethefatsi, athe li-receptors tsa mofuta oa II li ts'oaroa ka liphetoho tsa synaptic tse etsahalang ka lebaka la ho pepesehela lithethefatsi le li-syndromes tsa ho tlohela [21]. Kamora ho hlekefetsoa ha ntho efe kapa efe, ho fetisoa hoa glutamatergic ho hlaha tsamaisong ea limbic le cortex ea pele e shebahalang e na le boikarabello, pele ho tsohle, tokollo e kholo ea DA, le litlamorao tse tlisoang ke DA. Haholo-holo, le ha liketsahalo tse kang ho thefula maikutlo, ho lakatsa, ho khutlisa, le ho matlafatsa li hokahane le liphetoho tsamaisong ea dopaminergic le glutamatergic, maemo a ikhethileng le boits'oaro bo amanang le ts'ebeliso ea litheko haholo li its'etleha mekhoeng ea glutamatergic [22]. Ka bokhutšoanyane, tsamaiso ea glutamatergic-dopaminergic (bokong ba li-nucleus) e ikarabella ho qaleng ha "ho batla lithethefatsi," athe ho khutlela morao ho kenyelletsa feela tsamaiso ea glutamatergic [23]. Phokotso ea litheko tsa glutamate ea extracellular libakeng tsa maoto le matsoho ho bonahala e amana haholo le ramatiki e tsoang ho psychostimulants; metabotropic glutamate receptor agonists e bonahala e khona ho fokotsa ho lakatsa le ho thibela ho oela hape ka mokhoa oa puseletso. Hape, bahanyetsi ba li-receptor tsa metabotropic ba sitisa litlamorao tsa bootsoa tsa koae, nicotine, joala, mme bahanyetsi ba NMDA ke bao e ka bang likhetho bakeng sa kalafo ea opiate, joala le li-syndromes tsa ho tlohela lintho [24].
PG e nkuoe e le ho fetoloa haholo ke boko ba DA le Glu, leha liphetho li fapane. DA e susumetsoa ke boits'oaro bo monate, bo matlafatsang, le boits'ebetso. Tlatsong ea lithethefatsi, data e ts'ehetsa ho ba teng hoa boemo ba hypodopaminergic maemong ohle a presynaptic le a postynaptic [25]. Le ha tokollo ea DA e ka tiisa ho ithuta [26, 27], Glu e kanna ea e-ba le tšusumetso ho li-neuroadaptations tsa nako e telele ho "corticostriatal circry" e bonts'ang karolo e ka tlase ea suburalate ea ho mamella tlokotsi ea ho khutla hape [2]. Glu e kenya letsoho ho ithuteng le ho hopoleng mme e ka kenya tšebetsong mefuta e fapaneng ea li-Glu receptors, ho kenyelletsa le li-receptor tsa NMDA tse hlahisitsoeng libakeng tsa boko tse nang le meputso ea potoloho [2]. Mekhahlelo ea Glu kahare ho khubu e bokellanang mekhoa ea ho batla moputso [2]. Batho ba betang ka ho fetesisa ba tlaleha maikutlo a matla nakong ea papali ea papali ea chelete, e ka bapisoang le "e phahameng" ts'ebelisong ea lithethefatsi, ka hona ba etsa hore ba tloaetse ho tsuba. Ntle le moo, litlaleho tsa pele li bonts'itse phokotso ea matla a hedonic ho arabela tlholisanong eo hangata e nkoang e le e khotsofatsang [28]. Ka papali ea chelete e tsoelang pele, tšusumetso ea sesosa sa boits'oaro e ea matlafatsoa mme e etsa hore ho ts'oaroe bocha ho felle ka ho lakatsa liketsahalo le ho ka ntlafatsa katlehong ea methapo ea DA. Khabareng, ho tsoela pele ho becha le ho feto-fetoha ha maikutlo ka nako ea liphetoho tsa DA ho ka lebisa ho neuroadaptation litseleng tsa mesolimbic-prefrontal glutamatergic [29]. Ho ja lithethefatsi tse sa foleng ho tsamaisana le neuroadaptation ea glutamatergic neurotransication ho ventral striatum le limbic cortex [30]. Ntle le moo, ho pepesetsoa hoa cue ho fumanoe ho ipapisitse le lipalo tse matla tsa li-neuron tsa glutamatergic ho tloha sebakeng sa pele sa "cortex" ho ea ho li-nucleus accumbens [31]. Boitšoaro bo pheta-phetoang bo lateloang haholo ke meputso bo eketsa maemo a Glu ea ho feta [32]. Phuputsong e 'ngoe, tekanyetso ea "cerebrospinal fluid" (CSF) ea glutamic le aspartic acid, tseo ka bobeli li ikopanyetsang li-receptors tsa NMDA, li ile tsa phahamisoa har'a bakuli ba PG ha ba bapisoa le lithuto tsa taolo [33]. Ho se leka-lekane ho Glu homeostasis ho tlisa liphetoho ho li-neuroplasticity tse sitisang puisano pakeng tsa cortex ea pele le li-nucleus tse bokellaneng, ka hona li rata ho nka karolo molemong oa boits'oaro ba ho batla moputso, joalo ka PG [34].
4. Maano a Phekolo ea Glutamatergic a ho becha ka Pathological
Ho thetsoa ha glutamatergic neurotransication ke ntho e nyane empa e ts'episang mokhoa oa ho nts'etsapele basebetsi ba ntlafalitsoeng ba kalafo bakeng sa kalafo ea lithethefatsi le boits'oaro ba boits'oaro [10, 35]. Bopaki bo boholo bo bokelletse bo bonts'a hore li-ligands tse sebelisang phetisetso ea glutamatergic le tsona li ka thusa ts'ebelisong ea bokhoba ba lithethefatsi, hammoho le lithahasello tse fapaneng tsa boits'oaro tse joalo ka papali ea chelete. Bopaki bo ntseng bo hola bo bontša hore tsamaiso ea glutamatergic e bohareng ba neurobiology le kalafo ea mathata a maikutlo [36] le hore e ka emela sepheo sa bohlokoa ho PG ka maemo a comorbid [37].
4.1. N-Acetylcysteine
N-Acetylcysteine (NAC), k'holeseterole ea cysteine le amino acid, e ka eketsa maemo a tsoang mokhoeng oa Glu bokong ba li-nucleus mme e bontšitse katleho ea mantlha ho phekola bokhoba ba lithethefatsi [38, 39]. NAC e ka hlohlelletsa li-receptor tsa Glu inhibitory, mohlomong tsa baka phokotseho ea tokollo ea synaptic ea glutamate. Boithuto ho lipalo tsa batho ba bonts'ang hore NAC e sebetsa hantle ho fokotsa boits'oaro ba ho batla moputso [40] le tlhaiso-leseling ea pele ho PG ea khothatsa.
NAC e fumanoe e sebetsa hantle ho fokotsa litakatso tsa papali ea chelete le boitšoaro (lintlha tse tlase ho Yale-Brown Obsessive Compulsive Scale e fetotsoe bakeng sa PG (PG-YBOCS) tekong e nyane ea kliniki [14]. Lithuto tsa PG tse mashome a mabeli a metso e supileng (basali ba 12) ba ile ba phekoloa libeke tse 8 le NAC (lethal dose e ne e le 1476.9 ± 311.3 mg / letsatsi). Ba arabelang ba ile ba khethoa ka mokhoa o sa hlalosoang teko ea ho khaotsa libeke tse 6 (NAC vs placebo). Liperesente tse phahameng haholo tsa lithuto tse tšoaroang ke NAC li ntse li kopana le litekanyetso qetellong ea thuto (83.3% ho NAC bapisoa le 28.6% sehlopheng sa placebo). Ntle le moo, RCT ea morao-rao e netefalitse bohlokoa ba ntlafatso ea boitšoaro ba NAC kalafong ea PG [15]. Boithuto bona bo ile ba etsoa lithutong tse 28 tse neng li itšetleha ka koae ea nicotine e kopaneng. Ba fumane kalafo ea boits'oaro mme ba fetoloa ka tšohanyetso ho ntlafatsoa le NAC (ho fihlela 3,000 mg / ka letsatsi) kapa placebo tekong e sa boneng mahlo ka bobeli. Nakong ea tlhahlobo ea ho qetela ea likhoeli tse 3, ho bile le phaello e kholo ea NAC bapisoa le placebo mehatong e matla ea papali ea chelete (PG-YBOCS).
Litaba tse ngata li lula li sa rarolloe. Motsoako o nepahetseng oa NAC bakeng sa PG ha o ntse o sa tsejoe. Motsoako o sebelisitsoeng ho augmentation-RCT o ne o phahame haholo ho feta o sebelisitsoeng thutong e fetileng. Ho latela data ea makolopetso ho litoeba, likhahla tsa NAC li thibela phetisetso ea Glu bokong ba nyutlelie ha ntho e kaholimo e le teng [41]. Ho fanoe ka thepa ea NAC glutamatergic le karolo ea glutamate ho ithuteng le mohopolong oa lits'ebetso tsa ho lemalla [42], ts'ebeliso ea eona e khothalletsoe bakuli ba tlalehang ba lakatsang ho becha le bakeng sa ba ts'oereng phetoho ea kelello le kelello.
4.2. Memantine
Memantine, mohanyetsi ea sa qothisanang lehlokoa le mokelikeli oa NMDA ea nang le thepa ea methapo ea kutlo, oa amoheloa bakeng sa lefu la Alzheimer mme o ntse a tsoela pele ho ithutoa ka mafu a fapaneng a kelello [43]. Ho bakuli ba PG memantine e fokotsehile lintlha tsa PG-YBOCS le nako eo ba e sebelisang papali ea chelete, hape e ntlafatsa ts'ebetso ea methapo e amanang le ho fetoha ha kelello [11]. Lithuto tse mashome a mabeli a metso e robong li ile tsa ngolisoa tekong ea libotlolo tse bulehileng tsa libeke tse 10. Kamora kalafo ea memantine (10-30 mg / ka letsatsi), lipalo tsa PG-YBOCS le lihora tse sebelisitsoeng ho becha li fokotsehile haholo. Ntle le moo, lithuto li bile le tlhahlobo ea tlhaiso-leseling kamora 'ho sebelisoa ha mosebetsi oa ho emisa le tšebetso ea maiketsetso (extradimensional (IDED)) ho lekola ho tsitsinyeha le maemo a ho feto-fetoha ha maemo, ka ho latellana. Qetellong ea thuto, ntlafatso e kholo ts'ebetsong ea IDED e fumanoe, mohlomong ka lebaka la phetisetso ea memantine ea phetisetso ea glutamatergic ho PFC [44]. Leha ho le joalo, hore na memantine e fana ka tšusumetso e kae ea eona mokhoeng oa ho becha ka lits'usumetso tsa ho itlhahisa kapa ho qobelloa ho ntse ho sa hlaka [45].
Phuputso ea nyeoe ea bongaka e tlaleha katleho ea memantine kalafong ea mokuli ea lilemo li 23 ea nang le bothata bo sa bonahaleng bo amang kelello, bokuli ba dysmorphic, le PG e matla [12]. Karabelo ea tliliniki e ile ea bonoa kamora libeke tse 8 tsa kalafo ea memantine, ka taolo e fetang ea papali ea chelete le ho se be le tsitsipano e sa lebelloang le boithabiso.
Memantine e bonahala e fokotsa thabo ea Glu le ho ntlafatsa ho nka liqeto. Ntle le moo, e bonts'a ts'episo kalafo ea matšoao a ho kula le a qobelloang ho bakuli ba PG [11, 45].
4.3. Amantadine
Amantadine, sethethefatsi se loantšang matlafatso se nang le liketso tse ling tsa dopaminergic neurotransmission, se se se hlahlobiloe ho phekola PG le mekhoa e meng e tlamang ea batho ba nang le lefu la Parkinson [9, 46]. Lintlha tse fapaneng li tlalehiloe mabapi le ts'ebeliso ea amantadine har'a bakuli ba lefu la Parkinson [47]. E fumanoe e bolokehile ebile e sebetsa ho bakuli ba 17 ba nang le PG, ba fokotsa kapa ba emisa litakatso tsa ho becha le boitšoaro ba bona [9]. Phuputsong e entsoeng ka sefapano amantadine e ne e amahanngoa le PG le mathata a mang a taolo ea tšusumetso [48].
Ntle le moo, phuputso e entsoeng nyeoeng e khothalelitse ts'ebeliso e ka bang teng ho phekoleng bakuli ba PG8]. Phetoho e kholo matšoao a papali ea chelete ea ho becha e bonts'a hore ho feto-fetoha ha meriana ka nako e le 'ngoe ea mekhoa ea glutamatergic le dopaminergic ho ka fokotsa ho becha ho PG, mohlomong ho khutlisetsa liphetoho tsa methapo ea methapo ea methapo ea methapo e thehiloeng ke boits'oaro bo bobebe [2].
4.4. Topiramate
Topiramate ke setlaela sa glutamatergic le lithethefatsi tsa pro-GABAergic tse fokotsang haholo boitšoaro bo susumetsang le ho qobelloa. E entse liteko mme ea fumaneha e sebetsa hantle ha e bapisoa le placebo mathateng ao ho ipepesetsa le ho lakatsa ho emela likarolo tsa mantlha, joalo ka ho ts'epa joala, ho ts'epa k'hok'heine, bulimia manthaosa le bothata ba ho ja. Ntle le moo, ho sa tsoa etsoa tlhahiso ea hore topiramate hape e be mohanyetsi oa li-receptors tsa AMPA, e leng Glu receptor subtype e arolelanang boits'oaro bo tšoanang le boits'oaro mme e bohlokoa ho liphetoho tsa neuroadaptive tse hlahisoang ke lithethefatsi tsa tlhekefetso hape [49].
Beke e 14, e hlophisitsoeng ka boomo, e foufetseng habeli, e laoloang ke placebo e fuputse topiramate ho PG [17]. Leha ho sena liphapang tse kholo lipakeng tsa sehlopha sa placebo le sehlopha se tšoaroang ke topramate li ile tsa bonoa mabapi le mehato ea sephetho sa mantlha (phetoho ho subscale subscale ea PG-YBOCS), topiramate e fokolitse ho ts'oaroa haholo (haholoholo, koloi le ho hloka botsitso), joalo ka ha ho lekantsoe le le Barratt Impulsiveness Scale (BIS). Bangoli ba fana ka maikutlo a hore topiramate e ka ba molemo ho li-subgroups tsa PG tse tšoauoang ka maemo a phahameng a tšusumetso. Dannon et al. [16] bapisa katleho ea topiramate bapisoa le fluvoxamine kalafong ea PG tekong ea libeke tse 12, e bapisang mahlo. Leha bangoli ba phethela ka hore li-monotherapies tsa topiramate le fluvoxamine li ka sebetsa hantle kalafong ea PG, ntlafatso ho PG-CGI bakeng sa fluvoxamine ha ea ka ea fihlela bohlokoa ba lipalo. Hape, palo e nyane ea ba tlohang sekolong e tlalehiloe sehlopheng sa topiramate.
Ntle le moo, ho mokuli ea nang le lefu la ho ferekanya kelello le comorbid PG, Nicolato et al. [18] e tlaleha tšoarelo e felletseng ea takatso ea papali ea chelete le boitšoaro ka mor'a hore topiramate e eketsoe kalafo e tloaelehileng ea lithium.
4.5. Acamprosate
Acamprosate (calcium acetylhomotaurinate) ke taurine e tsoang le agonist e sa tsitsang ea GABA e khothalletsang ho leka-lekana lipakeng tsa li-neurotransmitters tse nyarosang (Glu le GABA). E tlama ka ho khetheha ho li-receptor tsa GABAB mme e bonahala e thibela li-Glu receptors le ho thibela signeractive glutamatergic sign [50]. Leha ho na le bopaki bo bokelletsoeng bo bonts'ang hore acamprosate e kena-kenana le tsamaiso ea Glu ka ho hanyetsa mosebetsi oa li-receptor tsa NMDA [51], ts'ebetso ea ts'ebetso ea eona e ntse e sa hlaka. Liphumano tsa morao-rao li bonts'a ho kenya letsoho ha litsela tsa calcium "52]. Ho se lumellane hona ho kanna ha amana le lintlha tse kang tikoloho ea boko e hlahlojoang, sebopeho sa submit ea NMDA, boemo ba ho teba ha neuronal, le ho ba teng hoa li-neuromodulator tsa NMDA tse fapaneng tsa morao-rao tse kang polyamines [50, 53]. Acamprosate e amohetse tumello ea tumello ea joala. Ho khutlisetsa ho leka-lekana lipakeng tsa thabo le khatello ea methapo e bakoang ke ho pepeseha hoa joala bo sa feleng [53], e fumanoe e phahamisa sekhahla se tsoelang pele sa ho itlopa joala le ho phethela matsatsi a ho khaotsa ho itlopa joala [54].
Liphetho tse fapaneng li tlalehiloe ts'ebeliso ea eona kalafong ea PG [55]. Bekeng e robeli, teko ea mabitso e bulehileng kamora ho bonoa libeke tse peli, acamprosate e ntlafalitse haholo lintlha tsa PG-YBOCS le Gossip Severity Assessment Scale (G-SAS), sekala ka bobeli sa CGI, le palo ea likarolo tsa papali ea papali ea chelete [6]. Bakuli ba mashome a mabeli a metso e tšeletseng ba fumane meriana eo (1,998 mg / ka letsatsi). Mohato oa mantlha oa katleho e ne e le PG-YBOCS. Lits'ebetso tsa ts'ebetso ea bobeli li kenyeletsa G-SAS, Sekala sa Ntlafatso ea Clinical Global Impressionment le Severity, tekanyo e ikemetseng ea boemo ba lefatše, boemo ba Hamilton Depression Rating Scale (HDRS), Sheehan Disability Scale (SDS), le tatellano ea tatellano ea nako. morao (TLFB).
Ho fapana le hoo, thuto e tšoanang e ile ea sitoa ho netefatsa katleho ea eona mabapi le boitšoaro ba papali ea chelete [7]. Thutong ena e bulehileng-label, bashemane ba 8 ba pathological ba tšoaroang ka acamprosate 999 mg / letsatsi ba ile ba hlahlojoa khoeli le khoeli bakeng sa likhoeli tse 6 ho hlahloba ho khutla hape. Ha ho na bakuli ba fumaneng likhoeli tse 6 tsa ho khaotsa ho tsuba, ho hlalosoang e le ho se be teng ha boitšoaro ba papali ea chelete nakong ea khoeli pele ho ketelo e latelang. Likolo tsa VAS qalong, kamora khoeli e le 'ngoe,' me ha motho a khutla hape li bontšitse hore ha ho na phapang ea bohlokoa lipalo. Ha ho likala tse netefalitsoeng tse sebelisitsoeng ho fumana katleho ea li-acamprosate litakatsong tsa ho becha le ho lakatsa.
4.6. Baclofen
Baclofen (beta- (4-chlorophenyl) -GABA) ke agonist ea GABAB e fumanoeng e hatella ho fumana boits'oaro ba lino tse tahang ka har'a likhoto le tšebeliso ea joala ea letsatsi le letsatsi litekong tse nang le joala. Ka ho thibela ho lokolloa ka bongata ho terminal ea presynaptic, e fokotsa ho ts'oana ha synaptic Glu [56] le ho thibela Ca2 + ho fumaneha ha li-receptor tsa NMDA. Litekong, e boetse e hatella ho tsoa ha dopamine e hlahisang joala ka khetla ea khubung ea li-nucleus bokellanang [57].
Teko e nang le lengolo le bulehileng [7], Bakuli ba 9 ba amohelang baclofen ba ile ba hlahlojoa khoeli le khoeli ho lekola mehato ea ntlafatso e tsoetseng pele (ke hore, ho ila) le ho oela hape. Ha ho na bakuli ba fumaneng likhoeli tse 6 tsa ho khaotsa ho tsuba, ho hlalosoang e le ho se be teng ha boitšoaro ba papali ea chelete nakong ea khoeli pele ho ketelo e latelang. ke mokuli a le mong feela ea fumanang baclofen ea fihletseng likhoeli tse 4 tsa ho khaotsa ho tsuba. Likolo tsa VAS qalong, kamora khoeli e le 'ngoe, hape ha motho a khutla hape li bontšitse hore ha ho na phapang ea bohlokoa lipalo.
4.7. Gabapentin le Pregabalin
Li-anticonvulsants, joalo ka gabapentin le pregabalin, li na le mekhahlelo e mengata e fapaneng ea ts'ebetso, ho kenyelletsa le inhibhibine ea "presynaptic voltage-gated Na + le Ca2 +", ka tsela eo e thibelang ho khutla ha li-neurotransmitters ho kenyeletsa le glutamate. Gabapentin modulates bobeli ba GABAergic le glutamatergic neurotransmissions. Bangoli ba 'maloa ba ithutile ts'ebeliso ea gabapentin mathateng a ts'ebeliso ea lithethefatsi. Gabapentin o khutlisetsa bofokoli ba GABA le monahano oa Glu o feteletseng oa ho itlhahisa joala le ho itlopa joala pele. E fokotsa tšebeliso ea joala le ho lakatsa, ka hona e nolofalletsang ho ila [58]. Pregabalin ke analog ea sebopeho sa GABA, e ts'oanang le gabapentin. E fokotsa le khatello ea methapo ea methapo ea kutlo le ho hlasimolla ka thabo. FDA e amohetse pregabalin bakeng sa lefu la sethoathoa, bohloko ba neuropathic, le mathata a ho tšoenyeha ka kakaretso. Ntle le moo, pregabalin e ithutile haholo ka ts'ebeliso ea joala le benzodiazepine [59]. Teko ea lifofane ea likhoeli tse 6 pele e ile ea etsa lipatlisiso mabapi le ts'ebeliso e ka bang teng ea ts'ebeliso ea bona ho bakuli ba PG (bakuli ba 6 ba amohela pregabalin; bakuli ba 4 ba amohetse gabapentin), ka phokotso ea litakatso tsa ho becha tse lekantsoeng ke G-SAS [10]. Hape, pregabalin e sebelisitsoe ho phekola nyeoe ea ho qaleha ho amanang le papali ea citalopram [60]. Boithuto ba nako e tlang bo lokela ho etsa lipatlisiso ka ts'ebeliso ea gabapentin le pregabalin kalafong ea PG, kaha setlhare sena se bonahala se shebile ka ho khetheha likarolo tse bohareng tsa ho susumetsoa, ho tšoenyeha le ho lakatsa.
4.8. Modafinil
Modafinil ke sehokahanyo sa atypical, eo qalong e neng e reretsoe ho ntlafatsa phaphama le ho falimeha kalafong ea lefu la narcolepsy 'me ka linako tse ling e fanoa e le kalafo e sa sebetseng bakeng sa tlhokomelo ea bofokoli / khatello ea kelello (ADHD). Le ha lits'ebetso tsa ts'ebetso li sa utloisisoe ka botlalo, modafinil ha e bonahale e sebetsa e le tlhahiso ea monoamine joalo ka maemo a kang a amphetamine. Ho fapana le moo, modafinil e ka sebetsa ka ho susumetsa α-adrenoceptors, e hatellang ho lokolloa ha GABA, e thibela ka mokhoa o fokotsang transporter ea dopamine, kapa e tsosang li-neurothalamic orexin tse nang le li-neurons [61, 62]. Le ha lithuto tse ngata li bontša motheo oa dopaminergic bakeng sa litlamorao tsa ona [63], modafinil e bontšitsoe ho phahamisa maemo a tsoang ho bokantle ba glutamate libakeng tse ngata tsa boko ho kenyeletsa dorsal striatum, hippocampus, le diencephalon ntle le ho ama synthetis ea glutamate [35, 64]. Litlaleho tse ngata tsa kliniki li bontšitse hore modafinil e bonts'a katleho e kholo kalafong ea ts'ebeliso ea lithethefatsi tsa koae [62].
Zack le Poulos [13], tekong e laoloang habeli ea bofofu e sa tsamaiseng mahlo, e lekile ho tseba hore na modafinil (e bolelang lethalamo la 200 mg / ka letsatsi) e fokotsa litlamorao tse matlafatsang tsa papali ea papali ea slot lithutong tsa PG le hore na phello e matla lithutong tse phahameng le tse tlase tse tsamaeang le (N = 20). Saese ea Bet e theohile ka mokhoa o ts'oanang ho barupeluoa ba phahameng le ba tlase ba nkang modafinil. Ho barupeluoa ba bangata ba sa tsubeng, modafinil o ile a fokotsa takatso ea ho becha, ho thella ha mantsoe a papali ea chelete, disinhibition, le ho etsa liqeto tse kotsi. Bakeng sa barupeluoa ba kenang ka tlase ho pherekano, modafinil e ile ea eketsa litheko ho indices tsena. Liphetho li bonts'itse hore modafinil o bile le litlamorao ho li-group tse peli. Mohlala o le mong oa bakuli o ile oa hlahlojoa bocha thutong e ka lebelloang, ka liphetho tsa bongaka tse totobatsang hore modafinil e ka nyahamisa batho ba tsubang ka methapo hore ba se ke ba lelekisa tahlehelo empa hape ba ba khothaletsa ho tsoela pele ho becha, ho fapana le ho tlohela ha ba ntse ba le pele65]. Hape, ho tlalehiloe nyeoe ea likamano tse hlakileng tsa nakoana pakeng tsa kalafo ea modafinil le papali ea methapo ho mokuli ea lilemo li 39 ea nang le nalane ea narcolepsy le cataplexy e amanang le eona [66].
5. Puisano
Ho na le bopaki bo bongata bo bonts'ang hore kalafo ea meriana e lebisang phetisetso ea glutamatergic ke ts'ebeliso e ka bang teng kalafong ea bokhoba ba lithethefatsi. Ka lebaka la hore lipatlisiso tsa methapo ea kutlo li bontša hore PG le bokhoba ba lithethefatsi li arolelana litsela tse tloaelehileng tsa etiopathological [5, 45], lithethefatsi tse lebisang phetisetso ea glutamatergic e kanna ea sebelisoa bakeng sa kalafo ea bokhoba ba boitšoaro (joalo ka, PG) hape.
Lintlha li bonahala li tiisa ts'ebeliso ea ho shebella tsamaiso ea glutamatergic bakeng sa kalafo ea PG, haholo ka ho nka khato ka ho lakatsa le ho eketsa ho boloka kalafo [10, 15]. Meriana ea Glutamatergic e ka u fa melemo e meng ea ho thibela ho oela hape [4]. Ho sa tsoa etsoa tlhahiso ea hore ts'ebeliso ea lithethefatsi e ka bonoa e le lebaka la bokhoni bo sitisang ho thibela lithethefatsi ho latela maemo a tikoloho, ka lebaka la liphetoho lipakeng tsa Glu homeostasis, hammoho le ts'ebetso e kopaneng ea li-receptors tse khothatsang tsa DA le NMDA [2]. Lithethefatsi tsa Glutamatergic li ka laola tšebelisano e rarahaneng pakeng tsa lits'ebetso tsa glutamatergic le dopaminergic, li sebetsa ka mokhoa o ts'oanang lits'ebetsong ka bobeli, ka mekhoa e hlokang ho hlahlojoa hamolemo.
Boithuto bo ithutoang ha bo na kutloisiso mabapi le mekhoa e sebelisitsoeng ho lekola katleho ea kalafo ea meriana bakeng sa PG. Ha e le hantle, lithuto tse ling li nka ho ba sieo ha boitšoaro ba papali ea chelete e le sephetho sa mantlha ha ho hlokomolohuoa likarolo tsa bohlokoa tsa kliniki ho kenyelletsa matšoao a ho lakatsa le ho tlohela. Ho khahlisang, lipatlisiso mabapi le lithethefatsi tsa glutamatergic li totobatsa bohlokoa ba ho supa tlhokomelo ea bongaka ho khethollo le kalafo ea matšoao a kelello [29]. Batho ba betang ka mokhoa oa peto ba bonts'a mokhoa oa ho etsa liqeto o hlokomolohang litlamorao tse sa feleng bakeng sa ho fumana khotsofalo hanghang kapa phomolo metseng e seng monate e amanang le bokhoba ba bona. Mekhahlelo e fapaneng ea kelello le maikutlo e susumetsa ho etsa liqeto [11]. Liphetoho tsena (ke hore, tlhalohanyo ea kelello) li ka kenya letsoho khethong e khelohileng ho bakuli ba PG le tlhokomelong ea bothata, joalo ka ha bo sa netefatsoe ke matla a teng a kalafo ea kelello e shebaneng le ho fetoloa moelelo oa ho becha o sa utloahaleng [67]. Ho shebisisa boemo bona ba bongaka, ho pholletsa le maemo ohle a ferekanyang a meriana, e ka ba pono e sebetsang ea kalafo mme e hloka ho tsoela pele ho ithutoa.
Lithethefatsi tse ntlafatsang ho etsa liqeto le bokhoni ba ts'ebetso ea botsamaisi ha li tsejoe haholo ka lebaka la ho rarahana ha mesebetsi ena e nang le subprocesses e fapaneng (ke hore, moputso, kutloelo-bohloko ea kotlo, le ho ts'oaroa). Leha ho le joalo, ho ka pheha khang ea hore basebeletsi ba ikemiselitseng merero ena e tlase le bona ba ka ntlafatsa ho etsa liqeto. Ntle le moo, batsebi ba ntlafatso ea kelello joalo ka modafinil le bona ba ka ba le litlamorao, haholo lithutong tse phahameng tsa ho susumetsoa [13].
6. Menahano ea Bokamoso
Lintlha li bonahala li netefatsa ts'ebeliso ea ho shebella tsamaiso ea glutamatergic bakeng sa kalafo ea PG, haholo ka ho sebetsa ka litakatso tse nang le litabatabelo le ho ba le kelello. Le ha kalafo e netefalitsoeng ka matla bakeng sa PG e na le tšehetso e fapaneng, ha ho tsejoe ka mekhoa ea tsona ea ts'ebetso kapa hore na mekhoa e meng ea phekolo e ka sebetsa hantle joang ho batho ba itseng. Ho entsoe liphuputso tse 'maloa ho leka bonnete ba bahanyetsi ba opioid kalafong ea lefu lena,' me tlhahlobo ea liphatsa tsa lefutso kapa nalane ea lelapa ea joala e fanoe ho laola karabelo ho bahanyetsi ba opioid ho pholletsa le lihlopha tsa tlhahlobo ea mafu [68]. Ka mokhoa o ts'oanang, lithuto tsa nako e tlang li lokela ho etsa lipatlisiso tsa likarolo tsa tlhaho le tsa kelello tsa bakuli ba PG bao kalafo ea glutamatergic e loketseng. Motheong oa tsebo ea hona joale, re fana ka maikutlo mabapi le likarolo tsa bongaka le litaba tsa comorbidity tse ka thusang ho tataisa lingaka ha ho khethoa maano a loketseng a kalafo ea glutamatergic (Setšoantšo sa 2). Moetso ona o ka fana ka motheo le mabaka ho tataisa khetho ea litlhare tsa litlhare tsa lihlopha tse ling tsa bakuli ba PG. Patlisiso tse ling hape li hlokahala ho netefatsa algorithm ea kalafo eo re e khothalletsang.
Kamora ho tsamaisoa ha koae, ho ile ha bonoa Glu homeostasis ea konokono ea nucleus. Letšoao le khethollang la homeostasis ke ho fokotseha ha polelo le ts'ebetso ea morekisi e moholo oa Glu, GLT-1 [69]. Lithuto tsa nako e tlang li lokela ho lekola karolo ea tsona ho PG le ts'ebeliso ea lithethefatsi tse ka sebelisang ho fetolela polelo ea ba tsamaisang thepa ea Glu neurotransmitter ka ts'ebetso ea gene (ke hore, ceftriaxone) [70].
Ntle le Glu le DA, lintlha tse ling, tse kang brain-based neurotrophic factor (BDNF), li ka nka karolo ketsong ea li-agents tsa glutamatergic ho PG [71]. Lintlha tsa Neurotrophic li bontšitsoe hore li fetoloa ke liketsahalo tsa tikoloho maemong a fapaneng a psychopathological [72], mme karolo ea bona e netefalitsoe ho pathophysiology ea PG [73]. Lithuto tsa nako e tlang li lokela ho thusa ho utloisisa karolo e ka 'nang ea fetoha ea modumo oa glutamatergic maemong a li-neurotrophins ho bakuli ba PG.
Patlisiso ea nako e tlang e ka una molemo litekong tsa bongaka tse laoloang ke placebo ho hlahisa melemo ea 'nete ea lithethefatsi tsa glutamatergic bakeng sa kalafo ea PG. Ntle le moo, lipatlisiso tsa nako e tlang li ka u thusa ho tsoa ho mathata a meriana le ho kopana le mekhoa ea ho hlahisa leseli mabapi le karolo ea Glu ho pathophysiology ea PG. Patlisiso e ncha ea neurobiological PG e lokela ho kenyelletsa taolo e tšoanang, akhaonto ea litaba tsa comorbidity, le phapang lipakeng tsa likhetho tsa papali ea chelete. Patlisiso lipotsong tse ikhethileng, ka lebaka leo, li lebelletsoe ho fana ka leseli le fetang la pathophysiology ea lefu lena lihlopheng tsena mme mohlomong li lebise ho tsa kalafo tse lumellanang haholoanyane le tse sebetsang. Boithuto ba nako e tlang bo boetse bo tlameha ho shebana le khokahano e sebetsang pakeng tsa lits'ebetso tsa dopaminergic le glutamatergic, e le ho hlakisa mekhoa e rarahaneng ea neurobiological e thehileng nts'etsopele ea boitšoaro bo bobe ba ho becha.
khutsufalitsoeng
PG: | Papali ea papali ea chelete |
gloo: | Glutamate |
ka: | Dopamine |
NMDA: | N-methyl-d-aspartate |
AMPA: | α-amino-3-hydroxy-5-methyl-4-isoazole- propionic acid |
PELE: | Asiti ea gamma-aminobutyric |
CSF: | Cerebrospinal mokelikeli |
NAC: | N-acetylcysteine |
RCT: | Teko e laoloang ke lebitso |
PG-YBOCS: | Yale-Brown Obsessive Compaleive Scale e fetotsoe bakeng sa PG |
G-SAS: | Sekala sa Teko ea Tekanyetso ea Papali ea Chelete. |
Khohlano ea Lithahasello
Bangoli ba phatlalatsa hore ha ho na likhohlano tsa lithahasello mabapi le phatlalatso ea pampiri ena.
References