Effects of anti-epileptic drugs on glutamine synthetase activity in mouse brain

1 Glutamine synthetase (GS) is a key enzyme in the regulation of glutamate neurotransmission in the central nervous system. It is responsible for the conversion of glutamate to glutamine, and for the detoxification of ammonia . 2 We have investigated the effects of single and repeated intraperitoneal a dministration of a range of established and new anti-epileptic drugs on GS activity in mouse brain. 3 Four hours after the final dose, animals were sacrificed and the brains r emoved for analysis of GS activity. 4 Both single and repeated doses of phenytoin and carbamazepine were found to reduce enzyme activity (P<0.05). 5 Single doses of phenobarbitone, felbamate and topiramate were without eff ect, however repeated administration of these drugs dose-dependently reduce d GS activity (P<0.05). 6 Single and repeated doses of sodium valproate, vigabatrin, lamotrigine, g abapentin, tiagabine, levetiracetam and desglycinyl-remacemide were found t o have no effect on GS activity. 7 The reduction in enzyme activity demonstrated is unlikely to be related t o the anti-epileptic actions of these drugs, but may contribute to their to xicity.