Targeting Glutamatergic System los kho Kev Tiv Thaiv Kabmob: Tamsim No Taw Qhia thiab Qub Yav Tom Ntej (2014)

  • Biomed Res Int. 2014; 2014: 109786.
  • Luam tawm hauv internet 2014 Jun 12. doi:  10.1155/2014/109786

PMCID: PMC4075088

Qhov no tsab xov xwm tau ua lawm sau los ntawm lwm cov xwm hauv PMC.

Mus rau:

Abstract

Kev twv txiaj kev twv txiaj lossis kev twv txiaj kev twv txiaj tau txhais los ntawm DSM-5 raws li kev coj cwj pwm. Txog hnub tim, nws cov kab mob pathophysiology tsis to taub tag nrho thiab tsis muaj tshuaj FDA pom zoo kho rau kev twv txiaj. Glutamate yog tus thawj xibfwb tso tawm neurotransmitter hauv cov leeg hlwb thiab nws tau tsis ntev los no koom nrog pathophysiology ntawm kev coj tus cwj pwm. Hauv daim ntawv no, peb saib cov ntawv nyeem tam sim no nyob rau hauv chav kawm ntawm cov tshuaj uas ua raws li modulating glutamate system hauv PG. Ib qho ntawm 19 cov kev tshawb fawb tau suav nrog, raws li kev xam nrog thiab cais tawm. Clinical trial thiab case series siv cov tshuaj glutamatergic (N-acetylcysteine, memantine, amantadine, topiramate, acamprosate, baclofen, gabapentin, pregabalin, thiab modafinil) yuav nthuav tawm rau kev ua kom zoo ntawm kev coj cwj pwm ntawm kev twv txiaj thiab ntawm cov chaw kho mob ntsig txog (kev xav, tshem tawm , thiab kev txawj ntse tshwm sim) hauv cov neeg mob PG. Cov txiaj ntsig tau tham txog kom pom ntau ntxiv rau cov kab mob pathophysiology thiab kev kho mob ntawm PG. Hauv kev xaus, kev ntxias ntawm glutamatergic neurotransmission zoo li tau cog lus hauv kev txhim kho cov neeg ua haujlwm zoo rau kev kho mob kev twv txiaj. Cov kev tshawb fawb txuas ntxiv yuav tsum muaj. Thaum kawg, peb qhia txog yav tom ntej cov lus qhia thiab cov kev cov nyom hauv qhov chaw tshawb fawb no.

1. Tom qab

Kev twv txiaj kev twv txiaj (PG) yog tus cwj pwm los ntawm kev twv txiaj tsis tu ncua thiab tsis raug cai, uas tib neeg koom nrog kev twv txiaj tsis tu ncua thiab pheej rov ua dua li ntawm qhov kev twv txiaj txawm tias muaj qhov tsis zoo tshwm sim [1]. Kev twv txiaj kev cuam tshuam cuam tshuam 0.2 – 5.3% ntawm cov neeg laus thoob ntiaj teb; Cov kev puas ntsoog loj heev ntawm qhov kev coj xeeb ceem no feem ntau ua rau muaj kev puas tsuaj rau lub neej ntawm cov neeg mob thiab lawv tsev neeg. Txog niaj hnub no, tsis muaj FDA-pom zoo kev kho mob rau PG, txawm tias yuav luag ib xyoo kaum ntawm kev tshawb fawb ntau, thiab cov tswv yim kho tau zoo tseem nyuaj heev. Tsis ntev los no, PG tau muab tso rau hauv kev kuaj mob qeb ntawm kev siv tshuaj yeeb dej caw thiab quav tshuaj muaj yees nyob rau hauv 5th tsab ntawv qhia txog Kev Ntsuam Xyuas thiab Kev Tshuaj Ntsuam Xyuas Kev Puas Hlwb (DSM-V).

Glutamate (Glu) yog tus thawj coj ntawm txoj hlab hlwb (neurotransmitter) hauv lub paj hlwb. Nws tau nyuam qhuav hais tias kev quav yeeb tshuaj tuaj yeem raug pom los ntawm qhov tsis muaj peev xwm los tiv thaiv kev quav yeeb tshuaj rau kev teb rau kev tiv thaiv ib puag ncig, vim kev hloov pauv hauv Glu homeostasis, nrog kev ua ke ntawm rhiab heev dopamine (DA) thiab N-methyl-d- aspartate (NMDA) glutamatergic receptors [2]. Kev txwv ntawm kev tso tawm Glu tau tiv thaiv tshuaj nrhiav tus cwj pwm hauv cov tsiaj txhu thiab cov neeg mob uas muaj kev quav yeeb tshuaj [3, 4]. Cov chaw kuaj mob thiab kuaj mob hlwb zoo sib xws ntawm PG thiab quav tshuaj yeeb tshuaj [5] tawm tswv yim tias cov neeg mob PG yuav tau txais txiaj ntsig los ntawm cov tshuaj siv los kho kev quav tshuaj yeeb quav tshuaj thiab cov qauv pathophysiological rau kev thiav tshuaj yuav cuam tshuam rau PG ib yam.

Hauv daim ntawv no, peb rov xyuas cov ntaub ntawv tam sim no ntawm cov tshuaj uas hloov kho glutamatergic neurotransmission hauv PG. Peb kuj elucidate kev xav tam sim no ntawm neurobiology ntawm PG, tsom mus rau glutamatergic neurotransmission thiab nws txoj kev cuam tshuam nrog lwm cov neurotransmitters. Cov chaw sim tshuaj thiab rooj plaub sib hais uas siv cov tshuaj glutamatergic yuav nthuav qhia txog qhov kev ua ntawm kev twv txiaj thiab ntawm kev kho mob ntsig txog (kev nqhis, tshem tawm, thiab kev paub) hauv PG tus neeg mob. Cov txiaj ntsig yuav raug tham txog kom nkag siab ntxiv rau cov kab mob pathophysiology thiab kev kho mob ntawm PG. Thaum kawg, peb qhia txog yav tom ntej cov lus qhia thiab cov kev cov nyom hauv qhov chaw tshawb fawb no.

2. Txoj kev

Ob txoj kev tshuaj ntsuam xyuas tau raug cais nyob rau hauv qhov kev tshuaj xyuas no, ua raws tib phau ntawv tshawb nrhiav thiab khaws cov ntaub ntawv. Kev tshawb fawb kab ke muaj kev tshawb fawb hauv computer ntawm Medline, Scopus, thiab Google Scholar hauv lub Ib Hlis 2014. Tsuas yog cov kev tshawb fawb lus Askiv luam tawm hauv kaum xyoo dhau los tau raug tshuaj xyuas. Peb tau siv cov lus nug nram qab no: "gambl *" ua ke nrog "glutamate" thiab nrog cov npe ntawm glutamatergic neurotransmission-modulating agents suav nrog N-acetylcysteine, memantine, amantadine, acamprosate, topiramate, lamotrigine, baclofen, gabapentin, pregabalin, modafoleil, ruv dizocilpine, LY354740, D-cycloserine, methadone, thiab dextromethorphan. Cov kev tshawb nrhiav pib ua rau 99 cov txiaj ntsig. Peb mam li txhais tes tshawb cov ntawv pov thawj cuam tshuam ntawm txhua kab lus, suav nrog cov kev tshawb fawb ua ntej ntawm lub ncauj lus.

Ntawm 99 cov khoom muaj peev xwm, 19 tau suav nrog (Daim duab 1) raws li kev ntsuas hauv qab no: (a) teeb meem phiaj teeb meem yog PG; (b) kev paub daws teeb yog muaj; (c) kev tshaj tawm yog daim ntawv qub, tsis suav nrog kev txheeb xyuas; (d) txoj kev tshawb no yog neurobiological lossis kev tshawb fawb soj ntsuam ntawm PG kawm.

Daim duab 1 

Txheej txheem bibliographic.

rooj 1 qhia cov ntaub ntawv muaj feem cuam tshuam ntawm cov kab lus muaj nyob rau hauv txoj kev tshawb no: kev siv yeeb tshuaj, kev siv tshuaj, kev tsim qauv, cov qauv loj thiab cov neeg raug mob, cov hauv kev, cov txiaj ntsig kev txawj ntse, thiab nrhiav cov ntsiab ntawm kev twv txiaj.

rooj 1 

Cov chaw kuaj mob hauv chaw kho mob thiab cov teeb meem kev siv cov tshuaj glutamatergic los kho kev twv txiaj pathological.

3. Glutamatergic Kev Hloov Hauv Kev Coj Tus Cwj Pwm: Kev sib raug zoo rau kev twv txiaj

Glu yog qhov muaj feem ntau excitatory neurotransmitter hauv CNS thiab nws qhov kev ua yog tswj hwm los ntawm ob hom receptors: ionotropic (iGlu) thiab receptors metabotropic (mGlu). Lub ionotropic receptors yog ion channels uas, raws li Glu khi, nce rau hauv kev cuam tshuam ntawm sodium thiab potassium cations ua rau depolarization ntawm daim nyias nyias [19]. Lawv tau muab faib ua peb qhov subtypes: N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoazole-propionic acid (AMPA), thiab kainate. Cov metabotropic receptors yog G protein-coupled receptors thiab tau muab faib ua peb pawg (I, II, thiab III) raws li homology ntawm cov kab ntawv sib txuas, cov tshuab ntawm cov teeb liab kis, thiab lawv cov chaw muag tshuaj [20]. Cov metabotropic receptors feem ntau nyob hauv thaj chaw limbic thiab thaj chaw pem hauv ntej, uas tau tshwj xeeb hauv cov txheej txheem ntawm cov quav. Tshwj xeeb, cov txais ntawm pab pawg Kuv zoo li muaj lub luag haujlwm tseem ceeb hauv kev tswj hwm qhov kev tiv thaiv cov tshuaj tiv thaiv, thaum hom II cov neeg txais tau cuam tshuam nyob rau hauv cov kev hloov pauv uas tshwm sim vim yog raug ntev ntev rau cov tshuaj thiab hauv kev rho tawm syndromes [21]. Tom qab kev tsim txom ntawm ib yam khoom twg, nce glutamatergic kis tau tshwm sim nyob rau hauv qhov limbic system thiab prefrontal cortex uas zoo li lub luag haujlwm, thawj zaug thiab tseem ceeb tshaj, muaj kev tso tawm ntau dua ntawm DA, thiab tseem cuam tshuam los ntawm DA. Tshwj xeeb, thaum muaj tshwm sim xws li kev hnov ​​mob, kev nqhis, rov huam dua, thiab txhawb ntxiv tau txuas rau kev hloov hauv ob qho tib si dopaminergic thiab glutamatergic, cov ntsiab lus hais thiab cov cwj pwm ntsig txog kev siv tshuaj yeeb tshuaj feem ntau nyob ntawm glutamatergic mechanisms [22]. Qhov luv luv, glutamatergic-dopaminergic system (hauv nucleus accumbens) yog lub luag haujlwm rau qhov pib ntawm "kev nrhiav tshuaj," thaum rov tshwm sim tsuas yog siv lub kaw lus glutamatergic [23]. Kev txo qis qib ntxiv glutamate hauv thaj chaw limbic zoo li muaj feem cuam tshuam nrog kev rho tawm ntawm lub hlwb los ntawm psychostimulants; metabotropic glutamate receptor agonists zoo li muaj peev xwm txo kev nqhis thiab tiv thaiv kom rov qab los ntawm kev siv nyiaj. Tsis tas li, antagonists ntawm metabotropic receptors cuam tshuam rau kev coj cwj pwm ntawm cov yeeb dawb, nicotine, thiab cawv, thiab NMDA antagonists yog cov muaj peev xwm xaiv tau los kho opiate, cawv, thiab sedative ntsoos ntsoos syndromes [24].

PG tau pom tias yuav tau hloov kho feem ntau los ntawm lub hlwb DA thiab Glu, txawm tias kev tshawb pom yog sib txawv. DA muaj feem cuam tshuam rau qhov khoom plig, ntxiv dag zog, thiab ntxiv rau kev coj tus yam ntxwv. Hauv kev quav yeeb tshuaj, cov ntaub ntawv txhawb nqa lub hav zoov ntawm lub xeev hypodopaminergic ntawm ob qho tshuaj tiv thaiv presynaptic thiab kev ua si ntawm25]. Thaum tso DA yuav txhawb txoj kev kawm [26, 27], Glu tej zaum yuav raug cuam tshuam nyob rau hauv ntev ntev neuroadaptations hauv corticostriatal circuitry uas sawv cev rau putative neural substrate ntawm kev nyuaj siab kom rov tshwm sim [2]. Glu tau koom nrog kev kawm thiab cim xeeb thiab tuaj yeem ua kom txawv ntau hom ntawm Glu receptors, suav nrog NMDA receptors qhia hauv cheeb tsam paj hlwb suav nrog cov khoom plig sib luag [2]. Theem ntawm Glu nyob rau hauv lub nucleus accumbens mediate nqi zog-nrhiav tus cwj pwm [2]. Cov kev twv txiaj kev twv txiaj tshaj tawm cov kev xav zoo siab thaum lub sijhawm twv txiaj, piv rau "siab" hauv kev siv tshuaj, yog li ua rau lawv muaj kev pheej hmoo rau kev twv txiaj txuas ntxiv. Tsis tas li ntawd, cov ntawv qhia ua ntej pom tau txo qis zog ntawm lub zog hedonic hauv kev teb rau stimuli feem ntau pom tau tias qhov nqi zog [28]. Los ntawm kev twv txiaj txuas mus ntxiv, kev nkag siab ntawm tus xeeb ceem kom coj tus cwj pwm ntxiv dag zog thiab ua rau muaj kev cov nyom tsis zoo uas tuaj yeem ua rau cov kev xav tsis zoo thiab muaj peev xwm txuas ntxiv ntawm DA neurotransmission. Thaum kawg, kev twv txiaj txuas mus ntxiv thiab tom qab hloov kho DA neurotransmission tuaj yeem ua rau neuroadaptation nyob rau hauv mesolimbic-prefrontal glutamatergic pathways [29]. Kev noj tshuaj rau lub cev ntev ntev yog txuam nrog neuroadaptation ntawm glutamatergic neurotransmission hauv lub ventral striatum thiab limbic cortex [30]. Tsis tas li ntawd, cue raug pom tau pom nyob ntawm qhov muaj zog tuaj ntawm glutamatergic neurons los ntawm prefrontal cortex mus rau lub nucleus accumbens [31]. Kev coj ua rov qab ua tib zoo ua raws li kev muab khoom plig nce qib ntxiv Glu32]. Hauv ib txoj kev tshawb nrhiav, cerebrospinal kua (CSF) qib ntawm glutamic thiab aspartic acid, ob qho tib si uas khi rau NMDA receptors, tau nce siab ntawm cov neeg mob PG piv rau kev tswj hwm [33]. Qhov tsis txaus ntseeg ntawm Glu homeostasis ua rau muaj kev hloov pauv ntawm neuroplasticity uas cuam tshuam kev sib txuas lus ntawm lub prefrontal cortex thiab lub nucleus accumbens, yog li muaj kev koom tes hauv kev nrhiav khoom plig, xws li PG [34].

4. Glutamatergic Kev Kho Mob Hauv Cov Phiaj twv txiaj

Manipulation ntawm glutamatergic neurotransmission yog qhov tseem hluas tab sis cog lus tias txoj kev rau kev txhim kho cov kws kho kom zoo rau kev kho tshuaj thiab tus cwj pwm ntxiv [10, 35]. Cov pov thawj hnyav tau nthuav tawm qhia tias ligands ua yeeb yam rau glutamatergic kis tau tus mob kuj tseem muaj txiaj ntsig zoo hauv kev kho kev quav yeeb tshuaj, nrog rau ntau yam kev coj cwj pwm ntxiv xws li kev twv txiaj pathological. Cov pov thawj nce zuj zus qhia tau hais tias lub kaw lus glutamatergic yog qhov tseem ceeb ntawm cov neurobiology thiab kho cov kev mob siab ntsws [36] thiab hais tias nws tuaj yeem sawv cev rau lub hom phiaj tseem ceeb hauv PG nrog rau cov neeg mob comorbid [37].

4.1. N-Acetylcysteine

N-Acetylcysteine ​​(NAC), cysteine ​​prodrug thiab amino acid, tuaj yeem nce qib ntxiv ntawm Glu cov ntsiab lus hauv lub nucleus accumbens thiab tau qhia ua ntej kev ua tau zoo hauv kev kho cov khoom muaj yees [38, 39]. NAC tuaj yeem txhawb qhov kev tiv thaiv inhibitory metabotropic Glu receptors, tuaj yeem ua rau txo qis hauv qhov tso tawm ntawm glutamate. Cov kev tshawb fawb hauv cov nas tau qhia tias NAC ua haujlwm tau zoo hauv kev txo cov nqi zog-nrhiav tus cwj pwm [40] thiab cov ntaub ntawv ua ntej hauv PG muaj kev txhawb zog.

NAC tau pom tias muaj txiaj ntsig zoo rau kev txo qis kev twv txiaj thiab kev coj tus cwj pwm (cov qhab nia qis dua ntawm Yale-Brown Obsessive Compulsive Scale hloov pauv rau PG (PG-YBOCS)) hauv kev sim me me [14]. Nees-nees nkaum xya PG kev kawm (Cov poj niam 12) tau kho rau 8 lub lis piam nrog NAC (txhais tau tias koob yog 1476.9 ± 311.3 mg / hnub). Cov lus teb tau xaiv nyob rau hauv 6-lub lim tiam ob lub qhov muag dig muag tsis ua qhov kev sim (NAC vs placebo). Qhov feem pua ​​ntau dua ntawm cov ncauj lus nrog NAC tseem ua tau raws cov lus teb ntawm qhov kev kawm thaum kawg ntawm kev kawm (83.3% hauv NAC tiv thaiv 28.6% hauv cov pawg placebo). Ntxiv rau, RCT tsis ntev los no tau lees tias kev ua tau zoo ntawm NAC augmentation ntawm kev kho tus cwj pwm hauv kev kho PG [15]. Txoj kev tshawb no tau ua rau 28 cov kev kawm nrog koom ua ke nicotine dependence thiab PG. Lawv tau txais kev kho tus cwj pwm thiab tau xaiv rau kev kho ntxiv nrog NAC (txog 3,000 mg / hnub) lossis placebo hauv kev sim ob-dig muag. Thaum lub sijhawm 3-lub hlis dhau los, muaj cov txiaj ntsig tseem ceeb ntxiv rau NAC tiv thaiv cov placebo ntawm qhov kev twv txiaj loj tshaj (PG-YBOCS).

Muaj ntau yam teeb meem tseem tsis tau daws. Qhov zoo tshaj koob ntawm NAC rau PG tseem tsis tau paub. Cov koob tshuaj uas siv hauv txoj kev augmentation-RCT yog qhov pom tau tias siab dua li uas tau siv hauv kev kawm yav dhau los. Raws li cov ntaub ntawv tshaj tawm hauv cov nas, cov ntsiab lus tsawg dua ntawm NAC inhibit Glu kis tau tus mob hauv nucleus accumbens core thaum ntau dua suav tau qhov teebmeem no [41]. Muab NAC glutamatergic yam ntxwv thiab glutamate lub luag haujlwm hauv kev kawm thiab nco qab hauv cov txheej txheem ntxiv [42], nws tau siv tau thov rau cov neeg mob uas tshaj tawm kev ntshaw mus twv txiaj thiab rau cov uas tseem tab tom ntsib kev cuam tshuam nrog kev puas hlwb.

4.2. Memantine

Memantine, tus neeg tsis sib raug zoo ntawm NMDA receptor nrog neuroprotective cov khoom, tau txais kev pom zoo rau Alzheimer tus kab mob thiab tau nce hauv kev kawm txog ntau yam kev puas hlwb [43]. Hauv PG cov neeg mob memantine txo PG-YBOCS cov qhab nia thiab lub sijhawm siv kev twv txiaj, tseem txhim kho cov kev ua haujlwm neurocognitive ntsig txog kev hloov pauv [11]. Nees nkaum cuaj hom kawm raug cuv npe hauv 10-lub lim tiam qhib kev cim ntawm kev sim. Tom qab kev kho memantine (10 – 30 mg / hnub), PG-YBOCS cov qhab nia thiab cov sijhawm siv kev twv txiaj poob qis. Ib qho ntxiv, cov kev kawm ua ntej-thiab tom qab kev soj ntsuam kev txawj ntse siv lub luag hauj lwm nres-lub teeb liab thiab cov intradimensional / extradimensional (IDED) teeb tsa ua haujlwm los mus ntsuas qhov kev ua tsis tau zoo thiab kev txawj ntse, ntsig txog. Ntawm kev tshawb pom qhov kawg, qhov kev txhim kho tseem ceeb hauv IDID qhov kev ua haujlwm tau pom, tej zaum vim muaj kev hloov kho lub ntsej muag ntawm glutamatergic kis hauv PFC [44]. Txawm li cas los xij, qhov uas memantine ua rau nws muaj kev cuam tshuam rau kev coj cwj pwm ntawm kev twv txiaj los ntawm kev cuam tshuam ntawm kev ua tsis tau lossis kev yuam kom tseem tsis tau paub meej [45].

Kev soj ntsuam cov ntaub ntawv tshawb fawb qhia txog kev muaj txiaj ntsig ntawm memantine nyob rau hauv kev kho mob ntawm 23-xyoo tus neeg mob nrog qhov kev xav tsis txaus ntseeg, lub cev tsis ua hauj lwm, thiab PG hnyav [12]. Cov lus teb hauv cov chaw kuaj mob tau pom tom qab 8 lub limtiam ntawm kev kho memantine, nrog kev tswj hwm ntau dua ntawm kev twv txiaj thiab tsis tshua muaj kev ntxhov siab thiab kev zoo siab.

Memantine zoo li txo Glu excitability thiab txhim kho kev txiav txim siab impulsive. Ib qho ntxiv, nws qhia tau cog lus hauv kev kho mob ntawm kev txawj ntse thiab pom tus kheej hauv cov neeg mob PG [11, 45].

4.3. Amantadine

Amantadine, ib qho tshuaj tiv thaiv antiglutamatergic nrog rau kev ua ntxiv ntawm dopaminergic neurotransmission, tau raug soj ntsuam hauv kev kho PG thiab lwm yam kev coj tsis zoo hauv cov tib neeg uas muaj tus kab mob Parkinson [9, 46]. Cov ntaub ntawv tsis sib haum xeeb tau hais txog kev siv amantadine ntawm Parkinson cov neeg mob [47]. Nws tau pom tias muaj kev nyab xeeb thiab zoo hauv 17 cov neeg mob nrog PG, txo lossis txwv kev twv txiaj thiab tus cwjpwm [9]. Hauv kev tshawb nrhiav ib ntu ntu amantadine tau cuam tshuam nrog PG thiab lwm yam kev tswj lub siab tsis ncaj [48].

Ib qho ntxiv, ib qhov kev tshawb nrhiav pom tau hais tias qhov muaj peev xwm nyob hauv kev kho mob ntawm PG tus neeg mob [8]. Cov kev txhim kho tseem ceeb ntawm cov tsos mob ntawm kev twv txiaj qhia tias kev hloov kho sib txuam ntawm cov glutamatergic thiab dopaminergic cov tshuab yuav txo qis kev twv txiaj hauv PG, tejzaum nws thim rov qab neuroplasticity-based pathological kev txiav txim siab los ntawm kev coj tus cwj pwm [2].

4.4. Topiramate

Topiramate yog glutamatergic antagonist thiab pro-GABAergic tshuaj uas txo qis kev coj tus cwj pwm thiab kev yuam tsis ua haujlwm. Nws tau sim thiab pom tias muaj txiaj ntsig piv rau cov placebo hauv kev tsis haum uas ua rau lub cev tsis haum thiab nqhis xim sawv cev tseem ceeb, xws li kev haus dej cawv, kev quav yeeb tshuaj yeeb dawb, kev tsis txaus siab ntawm bulimia nervosa, thiab kev tsis txaus siab rau lub cev. Tsis tas li ntawd, tsis ntev los no nws tau npaj siab tias topiramate kuj yog qhov fab ntxeev ntawm AMPA receptors, Glu receptor subtype uas sib kho cov kev coj zoo li rov qab los thiab yog qhov cuam tshuam hauv cov kev hloov pauv neuroadaptive uas tsim los ntawm cov tshuaj ntawm kev tsim txom ib yam nkaus [49].

Ib lub 14-lub lim tiam, muaj kev xaiv, muaj ob lub qhov muag dig, qhov chaw tswj hwm kev sim tshuaj xyuas tau soj ntsuam topiramate hauv PG [17]. Txawm hais tias tsis muaj qhov sib txawv tseem ceeb ntawm cov placebo pab pawg thiab cov pab pawg topiramate-kho tau pom nrog txoj kev ntsuas qhov txiaj ntsig tseem ceeb (kev hloov ntawm qhov kev xav tau qis ntawm PG-YBOCS), topiramate txo impulsivity (tshwj xeeb, lub cev muaj zog thiab tsis ua kom tsis haum), raws li ntsuas nrog lub Barratt Impulsiveness Nplai (BIS). Cov kws sau ntawv tau hais tias cov tshuaj topiramate tuaj yeem yog qhov muaj txiaj ntsig hauv PG pawg neeg sib txawv los ntawm theem siab ntawm tus kheej tsis muaj zog. Dannon li al. [16] piv rau cov txiaj ntsig ntawm topiramate piv rau fluvoxamine hauv kev kho PG hauv 12-lub lim tiam, qhov muag tsis pom kev sib piv. Txawm hais tias cov kws sau ntawv xaus lus tias ob qho tib si topiramate thiab fluvoxamine monotherapies zoo rau kev kho PG, kev txhim kho ntawm PG-CGI rau fluvoxamine tsis tau ncav cuag tseem ceeb. Tsis tas li, tsawg tus naj npawb ntawm kev tso tawm tau qhia nyob rau hauv pawg saum toj kawg nkaus.

Ib qho ntxiv, hauv tus neeg mob uas muaj kev puas siab puas ntsws bipolar thiab comorbid PG, Nicolato li al. [18] qhia tag nrho kev zam ntawm kev twv txiaj ntshaw thiab kev coj ua tom qab topiramate tau ntxiv rau kev kho mob lithium.

4.5. Acamprosate

Acamprosate (calcium acetylhomotaurinate) yog ib qho taurine derivative thiab tsis muaj qhov tsis tseem ceeb GABA agonist uas txhawb nqa qhov sib npaug ntawm kev tso tawm thiab cov tshuaj tiv thaiv neurotransmitters (Glu thiab GABA). Nws khi tshwj xeeb rau GABAB receptors thiab zoo nkaus li thaiv Glu receptors thiab inhibit hutractive glutamatergic signaling [50]. Txawm hais tias muaj ntau cov pov thawj tawm tswv yim tias acamprosate cuam tshuam nrog Glu system los ntawm kev thaiv kev NMDA receptor kev ua si [51], nws cov tshuab ntawm kev txiav txim tseem tseem tsis meej. Cov kev tshawb pom tsis ntev los no qhia txog kev koom tes ntawm calcium-mediated pathways [52]. Cov tsis sib xws yog kab ntsig ntsig txog yam tseem ceeb xws li lub cheeb tsam lub hlwb tau tshuaj xyuas, NMDA receptor subunit muaj pes tsawg leeg, lub xeev ntawm neuronal excitation, thiab muaj ntau yam endogenous NMDA receptor neuromodulators xws li polyamines [50, 53]. Acamprosate tau pom zoo los ntawm FDA rau kev haus cawv haus cawv. Rov qab pib qhov tsis txaus ntawm kev tso tawm thiab tiv thaiv kom tsis txhob mob neurotransmissions los ntawm kev haus cawv mus ntev [53], Nws tau pom tias nce cov kev haus cawv tsis pub ncua ntxiv thiab ob hnub ntawm kev ua kom tsis txhob haus cawv los ntawm kev haus cawv [54].

Cov txiaj ntsig tsis pom tseeb tau qhia txog nws qhov kev siv PG kev kho mob [55]. Hauv 8-lub limtiam, qhib kev sib tw qhib cov ntawv tom qab 2-lub limtiam kev sojntsuam, acamprosate tseem ceeb tau zoo dua PG-YBOCS thiab Kev twvtxiaj Severity Scale (G-SAS) cov qhab-nees, ob daim Scale CGI, thiab tus lej ntawm kev twvtxiaj [6]. Nees nkaum rau cov neeg mob tau txais cov tshuaj (1,998 mg / hnub). Qhov ntsuas kev ua tau zoo xub thawj yog PG-YBOCS. Cov kev ntsuas thib ob ua tau zoo muaj xws li G-SAS, Kev Ntsuam Xyuas Thoob Ntiaj Teb Qhov Kev Tshawb Fawb (CGI) Kev Txhim Kho thiab Severity nplai, tus neeg mob tus kheej kev ntsuas thoob ntiaj teb, Hamilton Kev Ntsuam Xyuas Cov Phiaj Xwm Kev Nyab Xeeb (HDRS), Sheehan Disability Scale (SDS), thiab kev ncua sij hawm ua raws. rov qab (TLFB).

Hauv kev sib piv, txoj kev tshawb fawb sib law liag tsis tau lees tias nws cov txiaj ntsig ntawm kev twv txiaj [7]. Hauv qhov kev kawm qhib-daim ntawv lo no, 8 pathological kev twv txiaj tau kho nrog acamprosate 999 mg / hnub tau raug ntsuas txhua hli rau 6 lub hlis los ntsuas kev rov ua dua. Tsis muaj ib qho ntawm cov neeg mob tau nce 6 lub hlis ntawm kev tsis lees paub, txhais tias tsis muaj ib qho kev coj tus cwj pwm hauv kev twv txiaj nyob rau lub hlis ua ntej rov mus ntsib. VAS cov qhab-nees hauv lub hauv paus, tom qab 1 lub hli, thiab ntawm kev rov qab ua rau pom tsis muaj qhov sib txawv. Tsis pub siv nplai uas siv tau los txiav txim qhov ua haujlwm ntawm acamprosate ntawm kev twv txiaj yaum thiab yees.

4.6. Baclofen

Baclofen (beta- (4-chlorophenyl) -GABA) yog GABAB receptor agonist uas tau pom los tua ob leeg txoj kev haus dej haus cawv kom zoo nyob hauv nas thiab haus dej haus cawv txhua hnub hauv cov nas uas muaj cawv. Los ntawm inhibiting multiveicular tso tawm los ntawm presynaptic davhlau ya nyob twg, nws txo synaptic Glu signaling [56] thiab inhibits Ca2 + permeability ntawm NMDA receptors. Cov nas, nws kuj tseem noj cov tshuaj dopamine tawm rau hauv lub khauj khaum nucleus accumbens [57].

Hauv kev sim qhib cov ntawv cim [7], 9 cov neeg mob tau txais baclofen tau raug tshuaj xyuas ib hlis ib zaug txhawm rau ntsuas kev ntsuas ntawm kev txhim kho uas txuas ntxiv (piv txwv li, tsis raug) thiab rov mob dua. Tsis muaj leej twg ntawm cov neeg mob tau x XXX lub hlis ntawm kev tsis lees paub, txhais tias tsis muaj ib qho kev coj tus cwj pwm hauv kev twv txiaj nyob rau lub hli ua ntej rov mus ntsib; tsuas yog ib tus neeg mob tau txais baclofen attained 6 lub hlis ntawm kev tsis ua haujlwm. VAS cov qhab-nees hauv lub hauv paus, tom qab 4 lub hli, thiab ntawm kev rov qab ua rau pom tsis muaj qhov sib txawv.

4.7. Gabapentin thiab Pregabalin

Anticonvulsants, zoo li gabapentin thiab pregabalin, muaj ntau cov txheej txheem ntawm kev ua, suav nrog kev txwv tsis pub presynaptic voltage-gated Na + thiab Ca2 + channels, yog li inhibiting qhov rov cuam tshuam ntawm neurotransmitters suav nrog glutamate. Gabapentin modulates ob qho GABAergic thiab glutamatergic neurotransmissions. Ntau tus kws sau ntawv tau tshawb txog kev siv gabapentin hauv kev siv tshuaj yeeb dej caw. Gabapentin thim rov qab GABA kev ua tsis txaus thiab Glu ntau dhau los xav yuam kev haus cawv thiab ua kom tsis pub sib deev thaum ntxov. Nws txo cov kev haus cawv thiab cov nqhis cawv, yog li ua kom tsis pub sib luag [58]. Pregabalin yog ib qho qauv ntawm GABA, zoo ib yam li gabapentin. Nws kuj txo qhov tso tawm tsis txaus siab neurotransmitter tso tawm thiab postsynaptic excitability. FDA tau pom zoo pregabalin rau kev mob vwm ib nrab, mob neuropathic, thiab kho cov kev ntxhov siab kom dav. Ntxiv rau, pregabalin tau kawm ntau yam hauv kev haus dej cawv thiab benzodiazepine dependence [59]. 6-lub hlis sim kev sim ua ntej tshawb xyuas qhov muaj peev xwm ntawm lawv kev siv hauv PG cov neeg mob (6 cov neeg mob tau txais pregabalin; 4 cov neeg mob tau txais gabapentin), nrog kev txo qis kev twv txiaj ntshaw raws li ntsuas los ntawm G-SAS [10]. Kuj, pregabalin tau siv los kho cov teeb meem kev twv txiaj ntsig ntsig txog citalopram thaum pib [60]. Cov kev tshawb fawb yav tom ntej yuav tsum tshawb xyuas kev siv gabapentin thiab pregabalin hauv kev kho PG, vim tias cov tshuaj no zoo li tshwj xeeb tshwj xeeb rau lub hauv paus hauv kev tsis muaj zog, ntxhov siab, thiab nqhis.

4.8. Modafinil

Modafinil yog atypical stimulant, thaum xub thawj tsim los txhawm rau txhim kho kev paub tab thiab kev kub ntxhov ntawm kev kho mob ntawm narcolepsy thiab qee zaum sau tseg raws li kev kho cov ntawv sau rau kev saib xyuas-kev tsis txaus siab / hyperactivity tsis meej (ADHD). Txawm hais tias nws cov txheej txheem ntawm kev nqis tes ua tsis tau to taub tag nrho, modafinil tsis zoo li ua yeeb yam li monoamine releaser zoo li muaj rau cov tshuaj tiv thaiv amphetamine zoo li. Theej, modafinil yuav ua los ntawm kev ua kom rov zoo dua α-adrenoceptors, txwv tsis pub GABA tso tawm, qaug zog tiv thaiv dopamine thauj khoom, lossis txhawb kev kho hypothalamic orexin-muaj cov neurons [61, 62]. Thaum feem ntau cov kev tshawb fawb pom zoo rau lub hauv paus dopaminergic rau nws qhov cuam tshuam [63], modafinil tau pom tias kom nce qib ntxiv ntawm glutamate nyob rau ntau thaj chaw hauv lub hlwb suav nrog dorsal striatum, hippocampus, thiab diencephalon yam tsis cuam tshuam rau glutamate synthes [35, 64]. Cov ntaub ntawv hais txog kev soj ntsuam ntau tau pom tias modafinil qhia tau tias qhov kev ua tau zoo ntawm kev muaj yeeb dawb cocaine62].

Zack thiab Poulos [13], nyob rau hauv cov placebo-tswj ob lub qhov muag dig, sim los txiav txim siab yog tias modafinil (txhais tau hais tias koob tshuaj 200 mg / hnub) txo cov teebmeem kev muaj zog ntawm cov tshuab twv txiaj hauv PG kev kawm thiab yog tias cov nyhuv no muaj zog nyob hauv siab piv nrog qis impulsivity compound (N = 20). Thawj qhov coob tau poob qis hauv ob qho tib si siab thiab qis impulsivity cov koom nrog noj modafinil. Hauv cov neeg muaj kev tiv thaiv siab, modafinil tsis tshua muaj lub siab xav mus twv txiaj, muaj kev twv txiaj ntawm cov lus twv txiaj, kev txwv tsis pub, thiab qhov kev txiav txim siab pheej hmoo. Hauv cov neeg muaj qhov tsis muaj zog, modafinil nce cov qhab nia ntawm cov ntsuas no. Cov txiaj ntsig tau pom tias modafinil muaj cov teebmeem bidirectional ntawm ob pawg. Tib qho piv txwv ntawm cov neeg mob tau raug rov ntsuam xyuas hauv txoj kev kawm yav tom ntej, nrog cov txiaj ntsig kev soj ntsuam qhia tias modafinil yuav ua rau txo qis kev twv txiaj kev twv txiaj los ntawm kev poob nyiaj tab sis tseem yaum kom lawv twv nyiaj ntxiv, dua li txiav tawm thaum lawv ua ntej [65]. Tsis tas li, nws tau tshaj tawm cov xwm txheej ntawm kev txiav txim siab txog kev sib raug zoo ntawm kev kho mob modafinil thiab kev twv txiaj pathological hauv 39-xyoo tus neeg mob uas muaj keeb kwm ntawm narcolepsy thiab cuam tshuam cataplexy [66].

5. Kev sib tham

Muaj cov pov thawj ntau uas qhia tau hais tias kev kho tshuaj pharmacological tsom rau kev xa mus kis glutamatergic yog cov muaj peev xwm nyob hauv kev kho mob ntawm kev quav yeeb tshuaj. Tau hais tias kev tshawb pom neurobiological qhia tau hais tias PG thiab kev quav yeeb tshuaj muaj yees nrog txoj kev ua haujlwm etiopathological [5, 45], Cov tshuaj siv rau cov roj ntsha glutamatergic kis tau tus mob tuaj yeem siv rau kev kho mob ntawm kev coj tus cwj pwm (xws li, PG) ib yam nkaus.

Cov ntaub ntawv zoo li paub meej txog kev siv hluav taws xob ntawm lub hom phiaj glutamatergic kev kho mob ntawm PG, tshwj xeeb los ntawm kev ua yeeb yam ntawm kev nqhis thiab nce kev kho kom zoo.10, 15]. Glutamatergic tshuaj yuav, qhov tseeb, muab qee qhov zoo hauv kev tiv thaiv kev rov huam mob [4]. Nws tau nyuam qhuav tawm tswv yim hais tias kev quav yeeb tshuaj tuaj yeem raug pom los ntawm qhov tsis muaj peev xwm tiv thaiv kev quav yeeb tshuaj rau kev teb rau kev tiv thaiv ib puag ncig, vim muaj kev hloov pauv hauv Glu homeostasis, nrog kev ua haujlwm ntawm cov tshuaj tiv thaiv DA thiab NMDA glutamatergic receptors [2]. Glutamatergic tshuaj yuav tswj tau cov kev sib cuam tshuam ntawm cov glutamatergic thiab dopaminergic systems, ua yeeb yam rau ob qho tib si, hauv txoj kev uas xav tau zoo dua los tshawb nrhiav.

Cov kev tshawb fawb tau tham tsis yog homogeneous nrog rau cov qauv uas siv los ntsuas kev ua haujlwm ntawm kev kho tshuaj rau PG. Qhov tseeb, qee qhov kev tshawb fawb xav txog kev tsis mus twv txiaj ntawm tus cwj pwm twv txiaj thaum thawj qhov tseem ceeb thaum saib qhov tseem ceeb hauv tsev kho mob nrog rau kev nqhis thiab tshem tawm cov tsos mob. Qhov zoo siab, kev tshawb fawb ntawm cov tshuaj glutamatergic qhia qhov tseem ceeb ntawm kev taw qhia hauv kev kho mob rau txoj kev kuaj pom thiab kho cov tsos mob uas txawj ntse [29]. Cov kev twv txiaj kev twv txiaj tsuas ua tus qauv ntawm kev txiav txim siab uas pheej tsis saib xyuas qhov tshwm sim tsis zoo mus ntev txhawm rau kom tau txais kev txaus siab tam sim ntawd lossis pab kom dim ntawm cov xeev tsis cuam tshuam nrog lawv cov quav. Ntau yam ntawm cov kev paub thiab cov kev xav hauv lub siab cuam tshuam rau kev txiav txim siab [11]. Cov kev hloov pauv no (piv txwv li, kev txawj ntse ntawm lub cev tsis meej pem) tuaj yeem ua rau muaj kev xaiv ntau yam hauv cov neeg mob PG thiab kev saib xyuas ntawm qhov tsis sib haum, raws li qhia ncaj qha los ntawm qhov ua tau zoo ntawm kev txawj ntse tsom mus rau kev hloov tsis paub kev twvtxiaj [67]. Kev tsom cov phiaj xwm saib xyuas no, thoob plaws kev kho qhov muag tshuaj hauv lub hlwb glutamatergic, tuaj yeem yog qhov pom kev kho mob uas tseem ceeb thiab xav tau kev kawm ntxiv.

Cov tshuaj uas txhim kho kev txiav txim siab thiab kev ua haujlwm muaj peev xwm ua haujlwm tau paub tsawg dua vim tias qhov yooj yim ntawm cov haujlwm no muaj cov txheej txheem sib txawv (piv txwv li, cov nqi zog, kev rau txim, thiab kev ua tsis tiav). Txawm li cas los xij, nws tuaj yeem sib cav tias cov neeg sawv cev tsom mus rau cov txheej txheem tom qab no yuav hloov kev txiav txim siab zoo ib yam. Tsis tas li ntawd, txhim kho kev txawj ntse xws li modafinil kuj tseem yuav muaj txiaj ntsig zoo, tshwj xeeb yog hauv cov kev kawm siab tsis nco qab [13].

6. Yav Tom Ntej Kev Pom Zoo

Cov ntaub ntawv zoo li paub meej txog kev siv hluav taws xob ntawm lub hom phiaj glutamatergic kev kho mob ntawm PG, tshwj xeeb los ntawm kev ua yeeb yam ntawm kev nqhis thiab kev txawj ntse (kev paub tsis meej thiab qhov tsis paub meej). Thaum hais txog kev siv tshuaj rau PG muaj ntau qib kev pab txhawb, tsawg paub txog lawv cov kev ua ntawm cov haujlwm lossis cov kev kho tej zaum yuav ua haujlwm zoo dua li cas rau qee tus neeg. Ntau cov kev tshawb fawb tau ua los ntsuas qhov ua tau ntawm opioid antagonists hauv kev kho mob ntawm kev puas tsuaj, thiab kev tshuaj ntsuam keeb kwm lossis tsev neeg keeb kwm ntawm kev quav cawv tau raug tshuaj lom rau kev tswj hwm cov lus teb rau opioid antagonists hla kev kuaj mob pawg [68]. Ib yam li ntawd, cov kev tshawb fawb yav tom ntej yuav tsum tshawb xyuas qhov txheeb raws roj ntsha thiab lub siab ntawm PG cov neeg mob rau kev kho tus mob glutamatergic yog qhov tsim nyog. Raws li kev paub tam sim no, peb qhia cov chaw kho mob thaj chaw thiab cov teeb meem comorbidity uas tuaj yeem pab qhia cov chaw kho mob hauv kev xaiv cov phiaj xwm kev kho mob glutamatergic (Daim duab 2)). Tus qauv no yuav muab tau lub hauv paus thiab kev paub daws teeb meem los xaiv cov khw muag tshuaj hauv qee pab pawg neeg mob PG. Qhov kev tshawb nrhiav txuas ntxiv yog qhov tseeb uas peb xav tau kom paub meej cov kev kho mob uas peb xav tau.

Daim duab 2 

Cov chaw kho mob thiab cov teeb meem comorbidity hauv kev xaiv cov txheej txheem kev kho glutamatergic los kho kev twv txiaj pathological.

Ua raws li kev tswj hwm cocaine, cuam tshuam Glu homeostasis ntawm nucleus accumbens core tau pom. Ib qho kev sib cais ntawm lub tsev tsis sib haum xeeb yog qhov txo qis hauv kev hais tawm thiab kev ua haujlwm ntawm Glu transporter loj, GLT-1 [69]. Cov kev tshawb fawb yav tom ntej yuav tsum tshawb xyuas nws lub luag haujlwm hauv PG thiab lub peev xwm ntawm kev siv tshuaj uas ua los hloov cov kev qhia ntawm Glu neurotransmitter cov neeg thauj khoom los ntawm kev ua kom muaj gene (piv txwv li, ceftriaxone) [70].

Dhau li ntawm Glu thiab DA, lwm yam, zoo li lub hlwb los ntawm lub hlwb neurotrophic (BDNF), tuaj yeem koom nrog hauv kev ua ntawm glutamatergic cov neeg ua haujlwm hauv PG [71]. Neurotrophic yam tau pom tias yuav hloov kho los ntawm cov xwm txheej ib puag ncig hauv ntau yam kev mob hlwb [72], thiab lawv lub luag haujlwm tau lees paub hauv pathophysiology ntawm PG [73]. Cov kev tshawb fawb yav tom ntej yuav tsum pab nkag siab txog lub luag haujlwm ntawm glutamatergic kev hloov kho rau qib neurotrophins hauv PG cov neeg mob.

Cov kev tshawb nrhiav yav tom ntej yuav muaj txiaj ntsig los ntawm cov tshuaj placebo tshuaj xyuas kab mob kom paub tseeb cov txiaj ntsig zoo ntawm glutamatergic tshuaj rau kev kho mob ntawm PG. Ib qho ntxiv, kev tshawb nrhiav yav tom ntej tuaj yeem siv txiaj ntsig los ntawm kev sib tw pharmacological nrog cov txheej txheem neuroimaging los tso teeb rau Glu lub luag haujlwm hauv pathophysiology ntawm PG. Cov kev tshawb fawb neurobiological PG tshiab yuav tsum muaj cov kev tswj hwm tau sib luag, lees paub txog qhov teeb meem comorbidity, thiab kev sib txawv ntawm qhov nyiam kev twv txiaj. Kev tshawb nrhiav hauv pawg neeg tshwj xeeb, yog li ntawd, cia siab tias yuav muab kev pom ntau ntxiv rau cov kab mob pathophysiology ntawm cov kev tsis sib haum xeeb hauv cov pab pawg no thiab tej zaum yuav ua rau muaj kev kho ntau dua thiab siv tau zoo. Cov kev tshawb fawb yav tom ntej yuav tsum tsom mus rau kev ua haujlwm sib txuas ntawm dopaminergic thiab glutamatergic systems, thiaj li yuav ua rau pom lub teeb rau cov neurobiological mechanisms kev ua kom pom kev txhim kho ntawm kev coj cwj pwm tsis zoo ntawm kev twv txiaj.

abbreviations

PG:Kev xav txog kev twv txiaj
Glu:Glutamate
DA:dopamine
NMDA:N-methyl-d-aspartate
AMPA:α-amino-3-hydroxy-5-methyl-4-isoazole- propionic acid
GABA:Gamma-aminobutyric acid
CSF:Cov kab mob Cerebrospinal
NAC:N-acetylcysteine
RCT:Randomized-tshuaj mus sib
PG-YBOCS:Yale-Brown Obsessive Compulsive Nplai hloov kho rau PG
G-SAS:Twv Txiaj Ntsig Kev Ntsuam Xyuas Cov Teev Seem.
 

Teeb meem ntawm Cov Ntxhais

Cov sau phau ntawv tshaj tawm tias tsis muaj teebmeem txog kev xav txog daim ntawv no.

References

1. Hodgins DC, Stea JN, Grant JE. Kev twvtxiaj cuam tshuam. Lub Lancet. 2011;378(9806):1874–1884. [PubMed]
2. Kalivas PW. Lub glutamate homeostasis hypothesis ntawm kev quav tshuaj. Xwm Txheej Txheem Ntseeg. 2009;10(8):561–572. [PubMed]
3. Krupitsky EM, Rudenko AA, Burakov AM, li al. Antiglutamatergic cov tswv yim rau kev tshem tawm ethanol: sib piv nrog cov placebo thiab diazepam. Alcoholism: Soj ntsuam thiab kev tshawb nrhiav. 2007;31(4):604–611. [PubMed]
4. Rösner S, Leucht S, Lehert P, Soyka M. Acamprosate txhawb kev haus dej haus cawv, naltrexone txwv tsis pub haus dej ntau dhau: cov pov thawj los ntawm kev soj ntsuam meta nrog qhov tsis qhia tawm. Phau Ntawv Psychopharmacology. 2008;22(1):11–23. [PubMed]
5. Potenza MN. Lub neurobiology ntawm kev quav twv txiaj thiab quav yeeb tshuaj: tus txheej txheem cej luam thiab tshiab tshawb pom. Cov Kev Lag Luam ntawm Philosophical Lub Tsev Neeg muaj koob muaj npe B: Txheeb pom txog Biological. 2008;363(1507):3181–3189. [PMC dawb tsab xov xwm] [PubMed]
6. Dub DW, McNeilly DP, Burke WJ, Shaw MC, Allen J. Ib qho qhib kev sib hais ntawm acamprosate hauv kev kho cov kev twv txiaj pathological. Annals ntawm Chaw Kho Mob Chaw Kho Mob Puas Siab Ntsws. 2011;23(4):250–256. [PubMed]
7. Dannon PN, Rosenberg O, Schoenfeld N, Kotler M. Acamprosate thiab baclofen tsis tau muaj txiaj ntsig zoo rau kev kho mob ntawm kev twv txiaj pathological: kev kawm ua piv txwv ua ntej qhov muag sib piv. Cov Hauv Paus Ntawm Kev Puas Siab Ntsws. 2011; 2, tsab xov xwm 33 [PMC dawb tsab xov xwm] [PubMed]
8. Pettorruso M, Martinotti G, di Nicola M, li al. Amantadine hauv kev kho mob ntawm kev twv txiaj pathological: ib daim ntawv qhia. Cov Hauv Paus Ntawm Kev Puas Siab Ntsws. 2012; 3, tsab xov xwm 102 [PMC dawb tsab xov xwm] [PubMed]
9. Thomas A, Bonanni L, Gambi F, Di Iorio A, Onofrj M. Cov kev twv txiaj hauv kev twv txiaj hauv chaw nres tsheb yog txo los ntawm amantadine. Annals ntawm Neurology. 2010;68(3):400–404. [PubMed]
10. Pettorruso M, Conte G, Righino E, li al. 2876-Glutamatergic cov tswv yim hauv kev kho mob kev twv txiaj pathological: kev sim tshuaj ntsuam. European PsychiatryCov. 2013; 28 (ntxiv 1): 1 nplooj ntawv.
11. Grant JE, Chamberlain SR, Odlaug BL, Potenza MN, Kim SW. Memantine qhia kev cog lus hauv kev txo qis kev twv txiaj ntau thiab ua rau kev nkag siab tsis meej nyob rau hauv kev twv txiaj pathological: kev sim tshawb. Psychopharmacology. 2010;212(4):603–612. [PMC dawb tsab xov xwm] [PubMed]
12. Pavlovic ZM. Kev kho mob hlwb psychopharmacological ntawm kev tsis txaus ntseeg-compulsive tsis meej comorbid nrog lub cev dysmorphic teeb meem thiab pathological kev twv txiaj tsis meej. Phau ntawv Journal ntawm Neuropsychiatry thiab Chaw Kho Mob Neurosciences. 2011;23(3):E42–E43. [PubMed]
13. Zack M, Poulos CX. Qhov cuam tshuam ntawm atypical stimulant modafinil ntawm kev hais txog kev twv txiaj ib nyuag ntu hauv kev twv txiaj kev twv txiaj nrog kev sib tw siab. Phau Ntawv Psychopharmacology. 2009;23(6):660–671. [PubMed]
14. Grant JE, Kim SW, Odlaug BL. N-acetyl cysteine, glutamate-modulating agent, hauv kev kho mob ntawm kev twv txiaj pathological: kev sim tshuaj. Txheeb Lawm Psychology. 2007;62(6):652–657. [PubMed]
15. Grant JE, Odlaug BL, Chamberlain SR, li al. Kev sim, muab cov tshuaj placebo rau txoj kev sim ntawm N-acetylcysteine ​​ntxiv rau qhov kev xav txog qhov muaj txiaj ntsig rau cov neeg muaj txiaj ntsig nrog kev twv txiaj hauv kev twv txiaj. Cov Phau Ntawv Xov Xwm ntawm Kev Mob Hlwb. 2014;75(1):39–45. [PubMed]
16. Dannon PN, Lowengrub K, Gonopolski Y, Musin E, Kotler M. Topiramate tiv thaiv fluvoxamine kev kho mob ntawm kev twv txiaj pathological: kev kawm sib piv, tsis pom kev sib piv. Soj ntsuam Neuropharmacology. 2005;28(1):6–10. [PubMed]
17. Berlin HA, Braun A, Simeon D, li al. Ob qhov muag dig, qhov chaw tswj xyuas qhov tsis txaus siab ntawm topiramate rau kev twv txiaj pathological. Ntiaj teb Phau Ntawv Xov Xwm Txog Kev Puas Siab Ntsws. 2013;14(2):121–128. [PubMed]
18. Nicolato R, Romano-Silva MA, Correa H, Salgado JV, Teixeira AL. Lithium thiab topiramate koom haum hauv kev kho mob ntawm kev twv txiaj twv twv twv twv twv tau twv txiaj yuam pov thiab bipolar tsis sib haum. Lub Australian thiab New Zealand Journal of Psychiatry. 2007;41(7):628–629. [PubMed]
19. Dingledine R, Borges K, Bowie D, Traynelis SF. Lub glutamate receptor ion channels. Pharmacological Xyuas. 1999;51(1):7–61. [PubMed]
20. Conn PJ, Pin JP. Pharmacology thiab cov haujlwm ntawm kev noj cov zaub mov metabotropic glutamate. Kev Tshuaj Xyuas Txhua Xyoo ntawm Pharmacology thiab Toxicology. 1997; 37: 205-237. [PubMed]
21. Kenny PJ, Markou A. Qhov ua kom qis thiab qis ntawm kev quav tshuaj: lub luag hauj lwm ntawm cov zaub mov metabotropic glutamate. Kev lag luam hauv Pharmacological Sciences. 2004;25(5):265–272. [PubMed]
22. Tzschentke TM, Schmidt WJ. Glutamatergic cov txheej txheem nyob rau kev quav. Molecular Psychiatry. 2003;8(4):373–382. [PubMed]
23. Qhuas JL, Kalivas PW. Cocaine rhiab heev thiab yees: cov cwj pwm txawv rau dopamine thiab glutamate hauv nucleus accumbens. Phau ntawv Journal ntawm Cov Kab Mob Kis. 2001;20(3):43–54. [PubMed]
24. Heidbreder C. Novel kws tshuaj hauv lub hom phiaj rau kev tswj hwm kev quav yeeb tshuaj. European Journal of Pharmacology. 2005;526(1-3):101–112. [PubMed]
25. Melis M, Spiga S, Diana M. Lub tshuaj dopamine kev ua rau kev quav yeeb tshuaj: xeev hypodopaminergic. Thoob Ntiaj Teb Saib Xyuas Kev Keeb Kwm ntawm Neurobiology. 2005; 63: 101-154. [PubMed]
26. Berridge KC, Robinson TE. Dab tsi yog lub luag haujlwm ntawm dopamine hauv kev ua nqi zog: kev cuam tshuam rau cov nyom, txiaj ntsig kev kawm, lossis kev txhawb siab kev coj zoo? Kev Ntsuam Xyuas Kev Ntsuam Xyuas Lub Hlwb. 1998;28(3):309–369. [PubMed]
27. Potenza MN. Lub hauv paus loj npaum li cas yog dopamine rau kab mob kev twv txiaj lossis kev twv txiaj? Frontiers nyob rau hauv Behavioral Neuroscience. 2013; 7, tsab xov xwm 206 [PMC dawb tsab xov xwm] [PubMed]
28. Pettorruso M, Martinotti G, Fasano A, li al. Anhedonia hauv Parkinson cov neeg mob thiab nrog tsis muaj kev twv txiaj txog kev twv txiaj: kev kawm tswj kev tshawb fawb. Kev tshawb nrhiav kev puas hlwb. 2014;215(2):448–452. [PubMed]
29. van Holst RJ, van den Brink W, Veltman DJ, Goudriaan AE. Vim li cas tus neeg twv txiaj tsis yeej: kev tshuaj xyuas cov kev txawj ntse thiab neuroimaging tshawb pom hauv kev twv txiaj pathological. Neuroscience thiab Biobehavioral Xyuas. 2010;34(1):87–107. [PubMed]
30. McFarland K, Lapish CC, Kalivas PW. Prefrontal glutamate tso tawm rau hauv cov tub ntxhais ntawm lub nucleus accumbens mediates cocaine-vim raug yuam rov los saib xyuas kev coj cwj pwm ntawm yeeb tshuaj. Phau ntawv Journal ntawm Neuroscience. 2003;23(8):3531–3537. [PubMed]
31. LaLumiere RT, Kalivas PW. Glutamate tso tawm hauv lub nucleus accumbens core yog qhov tsim nyog rau kev nrhiav tshuaj yeeb dawb. Phau ntawv Journal ntawm Neuroscience. 2008;28(12):3170–3177. [PubMed]
32. McFarland K, Kalivas PW. Lub voj voog nruab nrab ntawm txoj kev kho kom haum xeeb ntawm kev siv tshuaj yeeb-tshuaj. Phau ntawv Journal ntawm Neuroscience. 2001;21(21):8655–8663. [PubMed]
33. Nordin C, Gupta RC, Sjödin I. Cerebrospinal kua amino acids nyob rau hauv kev twv txiaj pathological thiab tswj kev noj qab haus huv. Neuropsychobiology. 2007;56(2-3):152–158. [PubMed]
34. Kalivas PW, Volkow ND. Cov tshuaj tshiab rau kev quav yeeb tshuaj tiv thaiv zais hauv glutamatergic neuroplasticity. Molecular Psychiatry. 2011;16(10):974–986. [PMC dawb tsab xov xwm] [PubMed]
35. Txiv Roj MF, Cleva RM, Kalivas PW, Malcolm RJ. Glutamatergic tshuaj rau kev kho mob ntawm yeeb tshuaj thiab kev quav yeeb tshuaj. Pharmacology Biochemistry thiab Cwj Pwm. 2012;100(4):801–810. [PMC dawb tsab xov xwm] [PubMed]
36. Machado-Vieira R, Ibrahim L, Ntsej Muag ID, Zarate CA., Jr. Cov tshuaj tiv thaiv glutamatergic rau qhov cuam tshuam loj thiab kev puas siab puas ntsws bipolar. Pharmacology Biochemistry thiab Cwj Pwm. 2012;100(4):678–687. [PMC dawb tsab xov xwm] [PubMed]
37. di Nicola M, li al. Kev puas siab puas ntsws bipolar thiab kev twv txiaj tsis meej: tam sim no cov pov thawj thiab cuam tshuam nrog kev kho tshuaj. Phau Ntawv Txheeb Txog Kev Xiam HlwbCov. Hauv xovxwm.
38. Baker DA, McFarland K, Lake RW, li al. Neuroadaptations hauv cystine-glutamate sib pauv underlie cocaine rov mob ntxiv. Qhov Nature Neuroscience. 2003;6(7):743–749. [PubMed]
39. Moran MM, McFarland K, Melendez RI, Kalivas PW, Seamans JK. Cystine / glutamate sib pauv tswj kev noj haus metabotropic glutamate receptor presynaptic inhibition ntawm excitatory kis thiab qhov tsis yooj yim mus nrhiav neeg nrhiav. Phau ntawv Journal ntawm Neuroscience. 2005;25(27):6389–6393. [PMC dawb tsab xov xwm] [PubMed]
40. Baker DA, McFarland K, Lake RW, Shen H, Toda S, Kalivas PW. N-acetyl cysteine-vim tau thaiv cov dej cawv ntawm cov neeg muaj yeeb dawb. Annals ntawm New York Academy ntawm Sciences. 2003; 1003: 349-351. [PubMed]
41. Kupchik YM, Moussawi K, Tang XC, li al. Cov nyhuv ntawm N-acetylcysteine ​​nyob rau hauv lub nucleus accumbens ntawm neurotransmission thiab rov mob rau cocaine. Txheeb Lawm Psychology. 2012;71(11):978–986. [PMC dawb tsab xov xwm] [PubMed]
42. Kalivas PW, O'Brien C. Kev quav tshuaj yeeb quav tshuaj raws li kab ke ntawm staged neuroplasticity. Neuropsychopharmacology. 2008;33(1):166–180. [PubMed]
43. Sani G, Serra G, Kotzalidis GD, li al. Lub luag haujlwm ntawm memantine nyob rau hauv kev kho mob ntawm kev puas siab puas ntsws uas tsis yog kev dementias: kev tshuaj xyuas cov pov thawj yav dhau los thiab cov pov thawj. CNS Tshuaj. 2012;26(8):663–690. [PubMed]
44. Van Wageningen H, Jørgensen HA, Specht K, Hugdahl K. A 1H-MR spectroscopy kawm txog kev hloov pauv hauv glutamate thiab glutamine (Glx) ntau nyob rau hauv frontal spectra tom qab kev tswj hwm ntawm memantine. Kab Cortex. 2010;20(4):798–803. [PubMed]
45. Leeman RF, Potenza MN. Qhov sib thooj thiab kev sib txawv ntawm kev twv txiaj thiab kev quav tshuaj yeeb dej caw: ib qho tseem ceeb ntawm kev ua tsis taus thiab sib txeeb. Psychopharmacology. 2012;219(2):469–490. [PMC dawb tsab xov xwm] [PubMed]
46. Fasano A, Ricciardi L, Pettorruso M, Bentivoglio AR. Kev tswj ntawm punding nyob rau hauv Parkinson tus kab mob: ib qho qhib-daim ntawv lo cia kev soj ntsuam kev kawm. Phau ntawv Journal ntawm Neurology. 2011;258(4):656–660. [PubMed]
47. Seppi K, Weintraub D, Coelho M, li al. Lub zog tsis sib haum xeeb hauv zej zog-pov thawj tshuaj xyuas kev hloov kho tshiab: kev kho mob rau cov tsos mob tsis zoo ntawm Parkinson tus kab mob. Cov Kev Mob Teeb Meem. 2011;26(3):S42–S80. [PMC dawb tsab xov xwm] [PubMed]
48. Weintraub D, Sohr M, Potenza MN, li al. Amantadine siv cuam tshuam nrog kev tswj hwm lub siab tsis ncaj nyob hauv tus kab mob Parkinson hauv kev tshawb fawb hla kev. Annals ntawm Neurology. 2010;68(6):963–968. [PubMed]
49. Gass JT, Txiv Roj MF. Glutamatergic substrates ntawm kev quav tshuaj yeeb thiab quav dej caw. Biochemical Pharmacology. 2008;75(1):218–265. [PMC dawb tsab xov xwm] [PubMed]
50. De Witte P, Littleton J, Parot P, Koob G. Neuroprotective thiab tsis lees paub-txhawb kev cuam tshuam ntawm acamprosate: elucidating lub mechanism ntawm kev ua. CNS Tshuaj. 2005;19(6):517–537. [PubMed]
51. Rammes G, Mahal B, Putzke J, li al. Cov tshuaj tiv thaiv kev sib xyaw ua kom zoo li kev ua haujlwm tsis muaj zog NMDA-receptor antagonist, tab sis modulates NMDA-receptor subunit qhia zoo ib yam li memantine thiab MK-801. Neuropharmacology. 2001;40(6):749–760. [PubMed]
52. Spanagel R, Vengeliene V, Jandeleit B, li al. Acamprosate tsim nws cov kev cuam tshuam rov qab los ntawm calcium. Neuropsychopharmacology. 2014;39(4):783–791. [PMC dawb tsab xov xwm] [PubMed]
53. Kiefer F, Mann K. Acamprosate: nws ua li cas, qhov twg, thiab ua haujlwm rau leej twg? Cov txheej txheem ntawm kev nqis tes ua, kev kho hom phiaj, thiab kev kho tus kheej. Tam sim no Pharmaceutical Tsim. 2010;16(19):2098–2102. [PubMed]
54. Boothby LA, Doering PL. Acamprosate rau kev kho mob ntawm cawv quav. Pab soj ntsuam txog kev kho mob. 2005;27(6):695–714. [PubMed]
55. Raj YP. Kev twv txiaj ntawm acamprosate: rooj plaub hais qhia. Phau Tshuaj Hloov Psychiatry. 2010;71(9):1245–1246. [PubMed]
56. Chalifoux JR, Carter AG. GABAB receptor kev hloov kho ntawm kev ua haujlwm synaptic. Cov Kev Xav Tam Sim No hauv Neurobiology. 2011;21(2):339–344. [PMC dawb tsab xov xwm] [PubMed]
57. Addolorato G, Leggio L, Cardone S, Ferrulli A, Gasbarrini G. Lub luag haujlwm ntawm GABAB receptor system hauv kev quav dej cawv thiab kev ntxhov siab: tsom mus rau kev tshawb fawb thiab kev kho kom pom. Haus dej cawv. 2009;43(7):559–563. [PubMed]
58. Furieri FA, Nakamura-Palacios EM. Gabapentin txo cov kev haus cawv thiab nqhis dej: ib qho kev sib tw, ob lub qhov muag dig, tshuaj placebo. Phau Tshuaj Hloov Psychiatry. 2007;68(11):1691–1700. [PubMed]
59. Martinotti G. Pregabalin nyob rau hauv kev kho hlwb thiab kev quav tshuaj tiv thaiv: tshaj thiab kev xav. Xav Kom Paub Txog Cov Kws Tshuaj. 2012;21(9):1243–1245. [PubMed]
60. Cuomo I, Kotzalidis GD, Caccia F, Danese E, Manfredi G, Girardi P. Citalopram-cuam tshuam kev twv txiaj: cov ntaub ntawv qhia. Phau Ntawv Qhia Txog Kev Twv Txiaj. 2014;30(2):467–473. [PubMed]
61. Ballon JS, Feifel D. Kev tshuaj xyuas cov txheej txheem los ntawm modafinil: kev siv tshuaj kho mob thiab cov tswv yim ntawm kev nqis tes ua. Phau Tshuaj Hloov Psychiatry. 2006;67(4):554–566. [PubMed]
62. Martínez-Raga J, Knecht C, Cepeda S. Modafinil: ib qho tshuaj muaj txiaj ntsig rau kev quav yeeb dawb? Tshawb xyuas cov pov thawj los ntawm neuropharmacological, kev sim tshuaj thiab cov kev tshawb fawb. Tam sim no tshuaj saib xyuas kev siv tshuaj yaj yeeb. 2008;1(2):213–221. [PubMed]
63. Volkow ND, Fowler JS, Logan J, li al. Qhov cuam tshuam ntawm modafinil rau dopamine thiab dopamine kev thauj neeg hauv txiv neej tib neeg lub paj hlwb cov chaw soj ntsuam. Phau ntawv Journal ntawm lub American Medical Association. 2009;301(11):1148–1154. [PMC dawb tsab xov xwm] [PubMed]
64. Ferraro L, Antonelli T, O'Connor WT, Tanganelli S, Rambert F, Fuxe K. Cov tshuaj antinarcoleptic modafinil ntau ntxiv glutamate tso rau hauv thaj chaw thalamic thiab hippocampus. NeuroReport Qhia tawm. 1997;8(13):2883–2887. [PubMed]
65. Ntse K, Desmond RC, Poulos CX, Zack M. Modafinil nce nqi zog zoo siab rau hauv kev siv lub tshuab ua si hauv qis qis thiab siab tsis tuaj yeem taug txoj kev twv txiaj. Neuropharmacology. 2013; 73: 66-74. [PubMed]
66. Tarrant N, Cavanna AE, Rickards H. Pathological kev twv txiaj txuam nrog modafinil. Phau ntawv Journal ntawm Neuropsychiatry thiab Chaw Kho Mob Neurosciences. 2010;22(1):E27–E28. [PubMed]
67. Ladouceur R, Sylvain C, Boutin C, Lachance S, Doucet C, Leblond J. Pab pawg kho mob rau cov kws twvtxiaj: txoj kev paub. Kev tshawb nrhiav tus cwj pwm thiab kho. 2003;41(5):587–596. [PubMed]
68. Grant JE, Kim SW, Hollander E, Potenza MN. Kev kwv yees teb rau opiate antagonists thiab cov placebo hauv kev kho mob kev twv txiaj pathological. Psychopharmacology. 2008;200(4):521–527. [PMC dawb tsab xov xwm] [PubMed]
69. Tanaka K, Watase K, Manabe T, li al. Epilepsy thiab exacerbation ntawm lub hlwb raug mob hauv cov nas uas tsis muaj cov glutamate transporter GLT-1. Science. 1997;276(5319):1699–1702. [PubMed]
70. Sari Y, Sakai M, Weedman JM, Rebec GV, Tswb RL. Ceftriaxone, ib qho tshuaj tua kab mob beta-lactam, txo kev noj tshuaj ethanol hauv cov dej cawv nyiam nyiam cov nas. Cawv thiab Cawv Cawv. 2011;46(3):239–246.agr023 [PMC dawb tsab xov xwm] [PubMed]
71. Jeanblanc J, Coune F, Botia B, Naassila M. Lub hlwb-ua tau neurotrophic qhov nruab nrab txwv tsis pub haus cawv rau kev tswj hwm tus kheej los ntawm memantine. Tshuaj Biology. 2013 [PubMed]
72. Angelucci F, Ricci V, Gelfo F, li al. Cov qib BDNF ntau ntau hauv cov ncauj lus txhim kho lossis tsis mob tom qab thaum muaj teeb meem rau tom qab raug mob. Hlwb thiab Cognition. 2014;84(1):118–122. [PubMed]
73. Angelucci F, Martinotti G, Gelfo F, li al. Txhim kho cov qib BDNF ntau ntau hauv cov neeg mob uas muaj kev twv txiaj txog kev twv txiaj heev. Tshuaj Biology. 2013;18(4):749–751. [PubMed]