Modulation of the antiepileptic activity of sodium valproate by lithium chloride against kainic acid and bicuculline-induced seizures

The influence of lithium chloride on the anticonvulsant activity of sodium valproate [VAL] was evaluated against two chemically-induced convulsive seizures; namely, bicuculline [BIC] and kainic acid [KAA]. Both drugs were given i.p., either singly or in combination to groups of mice [n = 8] and were allowed to act for 30 minutes before the chemical induction of seizures. Valproate was used in doses of 200 and 300 mg/kg [its ED50 against the specific convulsive agent] against BIC and KAA, respectively, whereas lithium chloride was used in a dose of 10 mg/kg. Then, convulsions were induced by i.p. injection of kainic acid [KAA, 70 mg/kg] and bicuculline [BIC, 1 mg/kg]. The animals were observed over a period of 40 minutes for the onset of convulsions. The mean survival time [MST] and the percentage of animals protected from death produced by each convulsive agent were computed. In conclusion, the present study suggested that the anticonvulsant action of sodium valproate against BIC and KAA-induced seizures may be partially augmented by the concurrent use of lithium chloride and this could be explained, at least in part, by the effect of lithium on the electrolyte levels caused by valproate

Some cardiovascular responses elicited by beta-adrenergic antagonists, calcium-entry blockers and their combinations

The present study was carried out on both intact rabbits and isolated perfused rabbit's heart for the assessment of the cardiovascular actions of Ca++ - entery blockers, beta blockers and their combinations. The results indicated that the Ca++ blockers, verapamil and nifedipine and the non selective beta blocker propranolol have a negative inotropic and chronotropic effects on the isolated heart preparation. The selective B-blocker atenolol, depressed the myocardium only in very high dose which is much greater than the therapeutic dose. The combinations of the two groups have an additive negative inotropic and chronotropic actions. The combinations of verapamil with the beta blockers, specially propranolol produced much more negative inotropic effect than when nifedipine was used instead of verapamil. The individual drugs of both groups have a hypotensive effect on the blood pressure [B.P.] of rabbits. The combinations of both groups of the drugs have no additive effect on the B.P. of rabbits. Electrocardiographic monitoring indicated that each verapamil, propranolol, atenolol and their combinations produced bradycardia and prolongation of both P-R and Q-T intervals. Nifedipine caused tachycardia and shortening of Q-T interval. The two groups of drugs produced insignificant changes in the electrolyte levels in serum and cardiac tissue except for Ca++ ion level in the cardiac tissue which was significantly reduced by the individual Ca++ blocking drugs and by their combination with the B-blockers