Article date: 1989/2/28
PubMed ID: 2542044
Journal name: European journal of pharmacology (ISSN: 0014-2999)
The effect of zolpidem, an imidazopyridine derivative with high affinity at the type I benzodiazepine recognition site, on the function of the GABAA/ionophore receptor complex was studied in vitro. Zolpidem, mimicking the action of diazepam, increased [3H]GABA binding, enhanced muscimol-stimulated 36Cl- uptake and reduced [35S]TBPS binding in rat cortical membrane preparations. Zolpidem was less effective than diazepam on the above parameters. Zolpidem induced a lower increase of [3H]GABA binding (23 vs. 35%) and muscimol-stimulated 36Cl- uptake (22 vs. 40%) and a smaller decrease of [35S]TBPS binding (47 vs. 77%) than diazepam. The finding that zolpidem enhanced the function of GABAergic synapses with an efficacy qualitatively and quantitatively different from that of diazepam suggests that this compound is a partial agonist at the benzodiazepine recognition site. Thus, our results are consistent with the view that the biochemical and pharmacological profile of a benzodiazepine recognition site ligand reflects its efficacy to enhance GABAergic transmission. Whether the preferential affinity of zolpidem at the type I site is involved in its atypical biochemical and pharmacological profile remains to be clarified.
Author List: Biggio G, Concas A, Corda M G, Serra M
Publication Types: Journal Article
Substances mentioned in the article: Bridged Bicyclo Compounds; Bridged Bicyclo Compounds, Heterocyclic; Hypnotics and Sedatives; Pyridines; Receptors, GABA-A; Muscimol; gamma-Aminobutyric Acid; tert-butylbicyclophosphorothionate; zolpidem; Diazepam;
Mesh terms: Animals; Bridged Bicyclo Compounds; Bridged Bicyclo Compounds, Heterocyclic; Diazepam/pharmacology; Hypnotics and Sedatives/pharmacology; Male; Muscimol/pharmacology; Pyridines/pharmacology; Rats; Rats, Inbred Strains; Receptors, GABA-A/metabolism; Synaptic Transmission/drug effects; gamma-Aminobutyric Acid/metabolism;