Effect of combined treatment of thioperamide with some antiepileptic drugs on methionine-sulfoximine induced convulsions in mice.

Methionine-sulfoximine (MSO), a convulsant is known to increase the activity of histamine N-methyl transferase. The effect of a selective H3 receptor agonist R- ( ) methylhistamine (RAMH) and antagonist (thioperamide, THP) and some antiepileptic drugs (gabapentin and sodium valproate) have been evaluated on MSO-induced convulsions in mice. The effect of THP was also evaluated in combination with these antiepileptic drugs. Sodium valproate (300 mg/kg, po) and gabapentin (400 mg/kg, po) offered protection against MSO-induced convulsions as evidenced by a significant prolongation of latency to abnormal dorsoflexion and complete protection against mortality within 6 h of administration. THP (15 mg/kg, ip) alone and in combination with sub-effective doses of gabapentin (75 mg/kg, po) and sodium valproate (75 mg/kg, po) revealed no significant differences from the control group or either drug alone. Hence, the convulsant action of MSO does not appear to be mediated via histaminergic mechanisms.