CLOBENPROPIT (VUF-9153), A NEW HISTAMINE H-3 RECEPTOR ANTAGONIST, INHIBITS ELECTRICALLY-INDUCED CONVULSIONS IN MICE

The effect of clobenpropit (VUF-9153), a new histamine H-3 receptor an tagonist, on electrically induced convulsions was studied in mice. Clo benpropit significantly and dose dependently decreased the duration of each convulsive phase. Its anticonvulsant effects were prevented by p retreatment with (R)-alpha-methylhistamine and imetit (VUF-8325), hist amine H-3 receptor agonists. These findings suggest that the effect of clobenpropit on electrically induced convulsions is due to an increas e in endogenous histamine release in the brain, which is consistent wi th biochemical results that clobenpropit increased brain histidine dec arboxylase activity dose dependently. The anticonvulsive effect of clo benpropit was antagonized by mepyramine, a histamine H-1 receptor anta gonist, but not by zolantidine, a histamine H-2 receptor antagonist, i ndicating that histamine released by the anticonvulsant effect of clob enpropit interacts with histamine H-1 receptors of postsynaptic neuron s. The present findings of the effect of clobenpropit on electrically induced convulsions are fully consistent with those of thioperamide as described previously (Yokoyama et al., 1993, Eur. J. Pharmacol. 234, 129), supporting the hypothesis that the central histaminergic neuron system is involved in the inhibition of seizures.