EFFECT OF CLOBENPROPIT, A CENTRALLY ACTING HISTAMINE H-3-RECEPTOR ANTAGONIST, ON ELECTROSHOCK-INDUCED AND PENTYLENETETRAZOL-INDUCED SEIZURES IN MICE

The anticonvulsant activity of clobenpropit, an isothiourea derivative of histamine and potent H-3-receptor antagonist, was investigated in two representative seizure models in mice. In the maximal electroshock seizure threshold test, clobenpropit dose-dependently raised the elec troconvulsive threshold for tonic (hindlimb extension) seizures, but a significant increase of about 15% was determined only at the high dos e of 40 mg/kg i.p. The protective action of this drug was reduced by i mmepip and (R)-alpha-methylhistamine, selective H-3-receptor agonists. In co-medication with two standard antiepileptics, clobenpropit (20 a nd 40 mg/kg) significantly increased the anticonvulsant effectiveness of carbamazepine and tended to increase the effectiveness of valproate . Additional studies indicated that the high dose of clobenpropit also significantly enhanced the plasma carbamazepine concentration. One th e other hand, in the s.c. PTZ seizure threshold test clobenpropit reve aled no protective effects. In the rotarod ataxia test, impaired motor function was observed at 80 mg/kg clobenpropit. In conclusion, the pr esent findings indicated no pronounced anticonvulsant effects of clobe npropit against generalized tonic as well as clonic seizures.