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.

Involvement of potassium channels in hypoglycemic effect of sertraline.

Effect of 21 days administration of sertraline (30 mg/kg, po) in streptozotocin (55 mg/kg, ip) induced diabetic and non-diabetic rats produced hypoglycemia in diabetic and non-diabetic rats. Pinacidil (1mg/kg, po), when co-administered with sertraline or glimepiride antagonized the decrease in glucose levels in diabetic rats. Pinacidil (10(-6)-10(-3) M) produced dose dependent relaxation (EC50-1.58 x 10(-5) M). Neither sertraline nor glimepiride had any effect on the resting tension of ileum preparation. Both sertraline and glimepiride antagonized competitively the pinacidil-induced relaxation. The pA2 values of sertraline and glimepiride reversal of pinacidil-induced relaxation were 5.5 and 6.2 respectively. These studies suggest the involvement of K+ channels in hypoglyceimic effects of sertraline.