Benzodiazepine Ro 15-1788: electrophysiological evidence for partial agonist activity.
The effects of diazepam and Ro 15-1788 were assessed upon responses of mouse spinal cord (SC) neurons in cell culture to the amino acid neurotransmitters 4-aminobutyric acid (GABA) and S-glutamic acid. Diazepam (100 nM) enhanced GABA responses by 65 +/- 3% (113 cells), while Ro 15-1788 (100 nM) failed to alter GABA responses but reduced their enhancement by diazepam. Higher Ro 15-1788 concentrations (1 microM or 10 microM) enhanced GABA responses to a moderate extent, while blocking further enhancement of GABA by diazepam. Neither diazepam nor Ro 15-1788 affected glutamate responses or resting membrane potential or conductance of spinal cord neurons. These results provide electrophysiological support for partial agonist, rather than pure antagonist, activity of Ro 15-1788.
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D046508:Culture Techniques; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005442:Flumazenil; D005727:Ganglia, Spinal / Q000187:drug effects; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000187:drug effects*; D011956:Receptors, Cell Surface / Q000187:drug effects*; D011963:Receptors, GABA-A; D013116:Spinal Cord / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D001570:Benzodiazepinones; D005971:Glutamates; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D018698:Glutamic Acid; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; D003975:Diazepam