Carbamazepine inhibits electroconvulsive shock-induced inositol trisphosphate (IP3) accumulation in rat cerebral cortex and hippocampus.

Carbamazepine is used to treat manic-depressive disorder, and is also an anticonvulsant. Rats were injected with this drug 90 min prior to this experiment, when mild inhibition of convulsions took place. Intraventricular injections of 14 muCi [3H]myoinositol were made 20-24 hrs prior to the experiment. Ninety min after intraperitoneal injection of carbamazepine or vehicle, rats were given electroconvulsive shock or sham procedure and sacrificed 30 sec later. Incorporation of radiolabel into inositol lipids and inositol phosphates was analyzed in cerebral cortex and hippocampus. Carbamazepine's effects on the brain inositol lipid cycle, studied here for the first time, showed 1) enhanced labeling in the polyphosphoinositides (carbamazepine-ECS groups showed increases of about 40% in PIP2); 2) decreased [H]IP1 levels; and 3) inhibition of ECS-induced [3H]-IP3 accumulation.