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Antagonism of the central effects of 3-methylclonazepam.

3-methylclonazepam is a new potent benzodiazepine which has been shown in clinical trials to be an effective schistosomicidal agent at high doses (Stohler, 1978). At the required schistosomicidal doses, however, effective therapy is offset by a high prevalence of typical benzodiazepine side-effects such as drowsiness, ataxia and muscle weakness. Ro 15-1788 (ethyl8-fluoro-5, 6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a] [1,4]-benzodiazepine-3-carboxylate) is a recently synthesised imidazodiazepine which antagonises the central effects of benzodiazepines at the receptor level (Hunkeler et al., 1981; Mohler & Richards, 1981). We have shown that 200 mg Ro 15-1788 effectively antagonises the potent sedative effects of 8 mg 3-methylclonazepam in healthy volunteers, when the substances were administered as a combined oral dose (Darragh et al., 1981). It has also been demonstrated that Ro 15-1788 is specific for the 'central' benzodiazepine receptor and does not antagonise the anti-schistosomal effect of 3-methylclonazepam in vitro or in vivo (Hunkeler etal., 1981). We have initiated a series of studies aimed at developing a combination dose of 3-methylclonazepam and Ro 15-1788 which would be an effective schisto-