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 administration 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 removed 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 effect, however repeated administration of these drugs dose-dependently reduced GS activity (P<0.05). 6. Single and repeated doses of sodium valproate, vigabatrin, lamotrigine, gabapentin, tiagabine, levetiracetam and desglycinyl-remacemide were found to have no effect on GS activity. 7. The reduction in enzyme activity demonstrated is unlikely to be related to the anti-epileptic actions of these drugs, but may contribute to their toxicity.
D000641:Ammonia / Q000378:metabolism; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D005974:Glutamate-Ammonia Ligase / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR