Antagonism of caffeine-induced seizures in mice by Ro15-1788.

The effect of the benzodiazepine antagonist Ro15-1788 has been tested against caffeine (200-300 mg/kg i.p.) induced convulsions in mice. It offered protection in lower doses (10 mg/kg i.p.) than had been effective previously against other convulsants such as bicuculline and leptazol. In contrast, diazepam was much less active against caffeine than against the other convulsants and offered no significant protection in doses up to 1 mg/kg i.p. If Ro15-1788 only acts on benzodiazepine receptors then one explanation for the increased activity of Ro15-1788 compared with diazepam against caffeine is that caffeine exerts its convulsant action through a direct effect on benzodiazepine receptors but is more potent at displacing diazepam than Ro15-1788 or alternatively it acts on a sub-class of benzodiazepine receptors that bind Ro15-1788 more effectively than diazepam.