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[Central effects of clonazepam].

The effects of oral administration of clonazepam, a new benzodiazepine derivative (F. Hoffmann-La Roche), on the central nervous system were compared with those of diazepam and several anticonvulsants in mice and rats. 1) Clonazepam exhibited a moderate inhibitory effect on the locomotor activity observed with open-field situation in mice and no effect in rats, while it inhibited markedly the rearing behavior in both animals, the duration of action being approximately six hours. 2) Clonazepam potentiated the methamphetamine-induced hyper-locomotor activity in mice whereas trimethadione had no effect. 3) Clonazepam inhibited with a moderate potency the conditioned avoidance response and response to a fixed-ratio (FR 20) schedule of food reinforcement in rats, the potency being a little weaker than that of diazepam. 4) The muscle relaxant effect of clonazepam determined by the traction test was slightly more potent as compared with that of diazepam. Thiopental hypnosis was markedly potentiated after clonazepam. 5) The clonic (CL), tonic-flexor (TF) and extensor convulsions (TE) induced by pentetrazol were strongly inhibited after clonazepam in mice, anticonvulsant potency against CL and TE of clonazepam being approximately 23 and 21 times stronger than that of diazepam, 3333 and 3846 times that of trimethadione, and over 3047 and 178 times that of phenytoin, respectively. Clonazepam reduced markedly CL and TE elicited by bemegride with about 12 to 14 times stronger potency than diazepam. On the contrary, the anticonvulsant effect of clonazepam against TE of maximal electroshock seizure evoked by supramaximal current was weak, the potency being 0.71 times weaker than that of phenacemide, 0.14 times than phenytoin and 0.24 times than phenobarbital. By the combined administration of clonazepam with other anticonvulsants such as trimethadione and phenytoin against pentetrazol convulsion, and phenacemide, phenytoin and phenobarbital against maximal electroshock seizure, the antagonistic effect of these anticonvulsants was potentiated by 4 to 5 times. 6) The acute toxicity (LD50) of clonazepam was weak but that of phenacemide or phenytoin was potentiated to a certain degree by combined administration with clonazepam. The results suggest that clonazepam has a psychopharmacological profile similar to that of benzodiazepines with a particularly potent anticonvulsant effect on pentetrazol and bemegride convulsions, and the anticonvulsant effect is synergic with that of other anticonvulsants.