Using Ro 15-1788 to investigate the benzodiazepine receptor in vivo: studies on the anticonvulsant and sedative effect of melatonin and the convulsant effect of the benzodiazepine Ro 05-3663.

Both the anticonvulsant and sedative effects of diazepam (5 mg/kg) were reversed by subsequent administration of the suggested specific benzodiazepine antagonist Ro 15-1788. In contrast neither the seizure threshold raising or sedative effect of melatonin (200 mg/kg) was reversed by Ro 15-1788. Ro 15-1788 had no effect on the convulsant action of the benzodiazepine Ro 05-3663. These data therefore argue against the suggestion that melatonin produces its sedative and anticonvulsant effects in vivo by interacting with the benzodiazepine receptor, and also strengthens the suggestion that Ro 05-3663 does not act at this site. The use of Ro 15-1788 in demonstrating whether a drug acts in vivo at the benzodiazepine site to produce a pharmacological response is discussed.