Electrophysiological and pharmacological characterization of peripheral benzodiazepine receptors in a guinea pig heart preparation.
RO5-4864 decreased in a dose-dependent manner, from 3 X 10(-9) M to 3 X 10(-6) M, the duration of intracellular action potential and the contractility in a guinea pig preparation. Diazepam was less effective and clonazepam inactive. The effects of RO5-4864 were GABA-independent and antagonized by PK 11195 but not by the selective antagonist of the brain type benzodiazepine receptors RO15-1788. These results show the pharmacological relevance of peripheral type benzodiazepine binding sites at the cardiac level.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D002998:Clonazepam / Q000494:pharmacology; D003292:Convulsants / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005442:Flumazenil; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011963:Receptors, GABA-A
D001570:Benzodiazepinones; D003292:Convulsants; D007546:Isoquinolines; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; C028513:4'-chlorodiazepam; D005442:Flumazenil; D002998:Clonazepam; D003975:Diazepam; C037850:PK 11195