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

الملخص EN

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 chemical induction of seizures.

Evaporate was used in doses of200 & 300 mg/kg (its ED50 against the specific convulsive agent) against BIC and KAA.

Respectively, whereas lithium chloride was used in a dose of10 mg/kg.

Convulsions were then induced by i.p.

injection of kainic acid (KAA 70 mg/kg) and bicuculline (BIC, I mg/kg).

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 then computed.

Results of the present investigation revealed that VAL alone was effective against seizures-induced by the two convulsive agents.

Significant increases in the onset of seizures, MST, and % protection of mice were recorded.

Administration of lithium chloride alone prolonged the MST and increased % protection of mice injected by BIC significantly while produced insignificant increase in % protection of mice injected by KAA.

Lithium chloride alone did not affect seizures onset in either types of convulsions.

Combined administration of lithium chloride and valproate led to an increase in each of, MST and % protection in mice injected with BIC, and only an increase in the MST of KAA-treated mice (compared with evaporate treated mice).

As regard serum and brain elyctrolytes (Na+ k+ and Ca+) levels there were some changes induced by the convulsant agents and the test drugs.

Serum and brain electrolytes (Na+, AT* and Ca2+) measurement revealed that combined administration of lithium chloride and VAL into mice subjected to the two test convulsive agents, compared with VAL, resulted in a) significant decrease in brain Na+ and increase in serum Ca2+ levels in mice injected with BIC, and b) significant diminution in brain Ca2* levels in mice following their injection with KAA..

The influence of lithium chloride on the anticonvulsant activity of valproic acid and their possible mechanism of action in modifying the convulsive activity produced by BIC and, KAA were discussed.