Interaction of pitrazepin with the GABA/benzodiazepine receptor complex and with glycine receptors.
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).
D000818:Animals; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002540:Cerebral Cortex / Q000378:metabolism; D003984:Dibenzazepines / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000378:metabolism; D009118:Muscimol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D018009:Receptors, Glycine; D017981:Receptors, Neurotransmitter / Q000187:drug effects* / Q000378:metabolism; D013331:Strychnine / Q000378:metabolism
D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003984:Dibenzazepines; D011963:Receptors, GABA-A; D018009:Receptors, Glycine; D017981:Receptors, Neurotransmitter; D009118:Muscimol; C037476:tert-butylbicyclophosphorothionate; C041662:pitrazepin; D013331:Strychnine