Abstract
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.
MeSH terms
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Action Potentials / drug effects
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Animals
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Benzodiazepinones / pharmacology*
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Clonazepam / pharmacology
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Convulsants / pharmacology*
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Diazepam / pharmacology
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Dose-Response Relationship, Drug
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Electric Stimulation
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Flumazenil
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Guinea Pigs
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Heart / drug effects
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In Vitro Techniques
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Isoquinolines / pharmacology*
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Myocardial Contraction / drug effects
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Myocardium / metabolism*
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Receptors, Cell Surface / metabolism*
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Receptors, GABA-A
Substances
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Benzodiazepinones
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Convulsants
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Isoquinolines
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Receptors, Cell Surface
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Receptors, GABA-A
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4'-chlorodiazepam
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Flumazenil
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Clonazepam
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Diazepam
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PK 11195