Diazepam and its anomalous p-chloro-derivative Ro 5-4864: comparative effects on mouse neurons in cell culture.
The actions of diazepam and its p-chloro-derivative Ro 5-4864 were compared on mouse spinal cord and dorsal root ganglion neurons in cell culture. Diazepam enhanced but Ro 5-4864 reduced iontophoretic GABA responses in a concentration-dependent manner. Both diazepam and Ro 5-4864 limited sustained, high frequency repetitive firing of spinal cord neurons but diazepam was more potent. Ro 5-4864 was, however, more potent than diazepam in inhibiting spontaneous neuronal activity of spinal cord neurons and reducing the duration of calcium-dependent action potentials of dorsal root ganglion neurons. The differing actions of diazepam and Ro 5-4864 may account for the contrasting pharmacological spectra of the two benzodiazepines.
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D002478:Cells, Cultured; D003292:Convulsants / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology*; D004347:Drug Interactions; D004622:Embryo, Mammalian; D005727:Ganglia, Spinal; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000187:drug effects*; D013116:Spinal Cord; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D001570:Benzodiazepinones; D003292:Convulsants; C028513:4'-chlorodiazepam; D005680:gamma-Aminobutyric Acid; D003975:Diazepam