MODULATION OF THE INTRACELLULAR AND H-3 HISTAMINE-RECEPTORS AND CHEMICALLY-INDUCED SEIZURES IN MICE

Central histaminergic modulation of H-1 rather than H-2-receptors has been shown to modify epileptic activity. Compounds acting on the H-IC- and H-3-receptors were tested against chemically-induced seizures in mice. Compounds antagonising the microsomal and nuclear intracellular receptors (H-IC) only modified seizures at doses where toxicity was ob served. Antagonists of the histamine H-3-receptor (thioperamide and bu rimamide) only potentiated the severity of clonic convulsions induced by picrotoxin, while impromidine (i.c.v.), an antagonist with H-2-agon ist activity, inhibited leptazol-induced seizures. The H-3-agonist, (R )alpha-methylhistamine, potentiated chemically-induced seizures, but a t lower doses there was slight inhibition.