Article date: 1985/11/26
PubMed ID: 3002806
Journal name: European journal of pharmacology (ISSN: 0014-2999)
Pitrazepin (3-(piperazinyl-1)-9H-dibenz(c,f)triazolo(4,5-a)azepin) is a new GABAA receptor antagonist reported to antagonize electrophysiological effects of GABA. We have investigated in some detail the interaction of pitrazepin with the GABA/benzodiazepine receptor chloride channel complex. Pitrazepin was found to be a competitive inhibitor of the GABAA receptor which is coupled to [3H]diazepam and [35S]TBPS binding sites; the KI value obtained by Schild analyses was 80 nM. Although pitrazepin interacted weakly with BZ receptors the compound did not affect the chloride gating mechanism (labelled with [35S]TBPS or [3H]avermectin B1a). Further, pitrazepin was a non-selective GABA antagonist since glycine receptors, labelled with [3H]strychnine, were affected at low concentrations (the KI values in rat brain-stem were 71-110 nM).
Author List: Braestrup C, Nielsen M
Publication Types: Journal Article
Substances mentioned in the article: Bridged Bicyclo Compounds; Bridged Bicyclo Compounds, Heterocyclic; Dibenzazepines; Receptors, GABA-A; Receptors, Glycine; Receptors, Neurotransmitter; Muscimol; tert-butylbicyclophosphorothionate; pitrazepin; Strychnine;
Mesh terms: Animals; Bridged Bicyclo Compounds; Bridged Bicyclo Compounds, Heterocyclic; Cerebral Cortex/metabolism; Dibenzazepines/pharmacology; In Vitro Techniques; Kinetics; Male; Membranes/metabolism; Muscimol/pharmacology; Rats; Rats, Inbred Strains; Receptors, GABA-A/drug effects; Receptors, Glycine; Receptors, Neurotransmitter/drug effects; Strychnine/metabolism;