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.