Muaj peev xwm siv tau rau GABA-Targeting Drugs tshiab hauv Kev Siv Dej Cawv

Kev siv GABA_B (GABA hom B) agonist, ADX71441, hauv kev sim ua ntej ua rau muaj kev txo qis hauv cawv. Cov tshuaj muaj zog txo qis kev mob siab rau haus thiab haus cawv nrhiav tus cwj pwm.

Gamma-aminobutyric acid (GABA) yog lub ntsiab inhibitory neurotransmitter¹. GABA yog ib qho ntawm cov neurotransmitters uas muaj nws cov teeb liab cuam tshuam los ntawm cawv² thiab nws yog ib qho tseem ceeb rau qhov tshwm sim ntawm cawv lub cev muaj zog. Kev tshawb nrhiav tsis ntev los no rau hauv GABA tshiab_B (GABA hom B) receptor zoo allosteric modulator (ib lub molecule uas khi rau thaj tsam ntawm ib qho chaw receptor sab nraud ntawm qhov chaw nquag ua kom muaj peev xwm ntawm cov molecules los khi rau cov receptor yog li ua kom cov receptors nce ntxiv) qhia tau tias muaj txiaj ntsig zoo hauv kev kho mob. cawv siv kev tsis sib haum xeeb¹.

GABA hom A (GABA_A) receptor tseem koom nrog cov teebmeem ntawm cawv ntawm lub hauv paus paj hlwb (CNS) raws li ethanol nce qhov kev txiav txim ntawm GABA ntawm GABA._A receptors³. Qhov no tau txhawb nqa los ntawm kev tshawb pom tias benzodiazepine, flumazenil, uas yog qhov tsis zoo allosteric modulator ntawm GABA._A receptor (lub molecule uas khi rau thaj tsam ntawm ib qho chaw receptor sab nraud ntawm qhov chaw ua haujlwm kom txo tau lub peev xwm ntawm cov molecules los khi rau cov receptor yog li txo qis kev ua kom cov receptor), thim rov qab cov teebmeem ntawm ethanol.³. Tsis tas li ntawd, flumazenil kuj tshem tawm qhov nce hauv kev ua phem thiab kev tsaug zog uas tau ntsib los ntawm cawv³ qhia tias GABA_A receptor kuj tseem cuam tshuam ntau rau hauv cawv cov teebmeem physiological thiab yog lub hom phiaj zoo ntawm kev thaiv ethanol-induced tus cwj pwm hloov.

Lub luag haujlwm ntawm GABA_B receptor hauv kev haus cawv kuj tau tshawb nrhiav, thiab GABA_B receptor agonist baclofen tau txais kev pom zoo raws li kev kho mob rau kev siv cawv nyob rau hauv Fabkis¹. GABA_B receptor agonists ua rau cov tshuaj tiv thaiv kab mob thiab anxiolytic, thiab baclofen yog siv los kho spasticity.¹. Baclofen txo qhov kev txhawb siab ntawm cov nas tsuag rau tus kheej tswj cov tshuaj tiv thaiv, tej zaum vim nws pom cov txiaj ntsig ntawm kev txo cov morphine, yeeb tshuaj yeeb thiab nicotine-induced dopamine tso tawm hauv cov nucleus accumbens.¹ qhov twg dopamine tso tawm ua rau muaj zog ntxiv ntawm kev coj cwj pwm⁴. Txawm li cas los xij, txawm tias GABA_B agonist baclofen lub peev xwm los pab kho kev siv cawv¹, baclofen muaj ntau yam kev phiv xws li sedation thiab tolerance-kev loj hlob qhia tias GABA_B receptor zoo allosteric modulators (PAMs) tuaj yeem tsim nyog rau kev sim nrhiav tshuaj nrog qhov ntsuas kho zoo dua¹.

Nov yog GABA_B PAM, ADX71441, hauv kev sim nas ua rau muaj kev txo qis hauv cawv kom tsawg (txog 65% nrog cov koob tshuaj ntau tshaj ntawm 200mg / kg)¹. Cov tshuaj muaj zog txo qis kev mob siab rau haus thiab haus cawv nrhiav tus cwj pwm¹, tawm tswv yim inhibition ntawm cawv-induced dopamine teb thiab yog li txo kev quav tshuaj. ADX71441 kuj ua rau muaj kev txo qis hauv cawv-nrhiav los ntawm ib puag ncig cawv-predictive ib puag ncig thiab raug rau kev ntxhov siab, qhia txog kev siv tshuaj kho mob los tiv thaiv kev siv cawv los ntawm ntau dua 50% ntawm cov neeg mob rov qab nyob rau hauv tsuas yog 3 lub hlis.¹. Cov kev tshawb fawb preclinical qhia qhov zoo tshaj ntawm GABA_B PAMs hais txog kev ua tau zoo rau cov kev mob tshwm sim. Qhov no ua pov thawj ntxiv kev tshawb fawb thiab kev sim kom coj tawm cov tshuaj tshiab los kho kev siv cawv¹ , yog li txo qis kev haus cawv uas ua rau lub nra hnyav rau kev noj qab haus huv thiab kev noj qab haus huv thoob plaws ntiaj teb.

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References:  

1. Eric Augier, Tsis ntev los no Ua Ntej Hauv Qhov Muaj Peev Xwm Zoo ntawm Allosteric Modulators ntawm GABA_B Receptor kho Cawv Kev Siv Dej Haus, Cawv thiab Cawv Cawv, Ntu 56, Nqe 2, Lub Peb Hlis 2021, Nplooj 139–148, https://doi.org/10.1093/alcalc/agab003 

1. Banerjee N. (2014). Neurotransmitters hauv cawv: Kev tshuaj xyuas ntawm cov kev tshawb fawb neurobiological thiab caj ces. Indian phau ntawv journal ntawm human genetics, 20(1), 20-31. https://doi.org/10.4103/0971-6866.132750 

3. Davies M. (2003). Lub luag haujlwm ntawm GABAA receptors hauv kev kho cov teebmeem ntawm cawv hauv lub hauv nruab nrab lub paj hlwb. Phau ntawv Journal of Psychiatry & neuroscience: JPN, 28(4), 263-274. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC165791/  

4. Science Direct 2021. Nucleus Accumbens. Muaj nyob rau https://www.sciencedirect.com/topics/neuroscience/nucleus-accumbens  

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