Modulation of the intracellular and H3-histamine receptors and chemically-induced seizures in mice

Central histaminergic modulation of H1 rather than H2-receptors has been shown to modify epileptic activity. Compounds acting on the HIC- and H3-receptors were tested against chemically-induced seizures in mice. Compounds antagonising the microsomal and nuclear intracellular receptors (HIC) only modified seizures at doses where toxicity was observed. Antagonists of the histamine H3-receptor (thioperamide and burimamide) only potentiated the severity of clonic convulsions induced by picrotoxin, while impromidine (i.c.v.), an antagonist with H2-agonist activity, inhibited leptazol-induced seizures. The H3-agonist, (R)alpha-methylhistamine, potentiated chemically-induced seizures, but at lower doses there was slight inhibition.