[Potential therapeutic activity of GABA-mimetic drugs in neuropsychiatry].
Several pieces of evidence support the view that GABA neurons inhibit the DA system both in extrapyramidal and limbic regions. This inhibition is exerted on cell bodies and terminals of DA neurons and is involved in the regulation of their activity. A recently synthesized GABAmimetic compound SL 76.002 has considerably helped in elucidating the role of GABA in this regulation as well as the therapeutic implication of changes of GABAergic transmission in human brain. Thus, impairment of dopaminergic transmission by SL 76.002 has been shown to be effective in iatrogenic extrapyramidal syndromes such as L-DOPA-induced involuntary movements in parkinsonian patients and neuroleptic-induced tardive dyskinesias: the first attributed to an exaggerated formation and liberation of DA, the second to supersensitivity of target cells of DA neurons. Furthermore, GABAergic medication has been confirmed to be useful in Huntington's chorea in which some symptoms originate from degeneration of striatal GABAergic neurons. Finally, GABAergic inhibition on cellular excitability has been proved to ameliorate epilepsy. However, SL 76.002, contrary to the expectation, was not effective in schizophrenia suggesting that GABA does not play a major role in the pathogenesis of this disorder.
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors; D001480:Basal Ganglia Diseases / Q000188:drug therapy* / Q000503:physiopathology; D001640:Bicuculline / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy; D004827:Epilepsy / Q000188:drug therapy; D005116:Extrapyramidal Tracts / Q000187:drug effects; D006801:Humans; D006816:Huntington Disease / Q000188:drug therapy*; D007980:Levodopa / Q000494:pharmacology / Q000627:therapeutic use; D008032:Limbic System / Q000187:drug effects; D009434:Neural Pathways / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000494:pharmacology / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy; D011600:Psychopharmacology; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use
D018377:Neurotransmitter Agents; C017985:progabide; D007980:Levodopa; D005680:gamma-Aminobutyric Acid; D000612:4-Aminobutyrate Transaminase; D004298:Dopamine; D001640:Bicuculline
Activité thérapeutique potentielle des drogues GABA mimétiques en neuropsychiatrie.