The turnover rate of gamma-aminobutyric acid in the nuclei of telencephalon: implications in the pharmacology of antipsychotics and of a minor tranquilizer.
The turnover rate of GABA is measured in substantia nigra, globus pallidus, N. accumbens, and striatum of rats injected with muscimol, a potent GABA agonist, and diazepam. The similarity of action of the two drugs on GABA turnover further supports the theory that diazepam acts as a GABA-mimetic drug. Haloperidol and clozapine affect GABA turnover differently in different nuclei. Haloperidol decreases GABA turnover in caudate but does not affect that in substantia nigra, whereas clozapine increases GABA turnover in both areas. However, both drugs accelerate GABA turnover in globus pallidus and N. accumbens. It is suggested that an increase of GABA turnover and perhaps of GABA release in striatum and substantia nigra may account for the lack of tardive dyskinesia and extrapyramidal side effects of clozapine.
D000613:Aminobutyrates / Q000378:metabolism*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002421:Caudate Nucleus / Q000378:metabolism; D003024:Clozapine / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism; D003975:Diazepam / Q000494:pharmacology; D005917:Globus Pallidus / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D010277:Parasympathomimetics / Q000494:pharmacology; D051381:Rats; D013378:Substantia Nigra / Q000378:metabolism; D013687:Telencephalon / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000613:Aminobutyrates; D014151:Anti-Anxiety Agents; D014150:Antipsychotic Agents; D005971:Glutamates; D010277:Parasympathomimetics; D005680:gamma-Aminobutyric Acid; D003024:Clozapine; D006220:Haloperidol; D003975:Diazepam