{"doi":"10.1038/sj.bjp.0702472","title":"Effects of anti‐epileptic drugs on glutamine synthetase activity in mouse brain","abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item>\n<jats:p>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.</jats:p>\n</jats:list-item>\n<jats:list-item>\n<jats:p>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.</jats:p>\n</jats:list-item>\n<jats:list-item>\n<jats:p>Four hours after the final dose, animals were sacrificed and the brains removed for analysis of GS activity.</jats:p>\n</jats:list-item>\n<jats:list-item>\n<jats:p>Both single and repeated doses of phenytoin and carbamazepine were found to reduce enzyme activity (<jats:italic>P</jats:italic>&lt;0.05).</jats:p>\n</jats:list-item>\n<jats:list-item>\n<jats:p>Single doses of phenobarbitone, felbamate and topiramate were without effect, however repeated administration of these drugs dose‐dependently reduced GS activity (<jats:italic>P</jats:italic>&lt;0.05).</jats:p>\n</jats:list-item>\n<jats:list-item>\n<jats:p>Single and repeated doses of sodium valproate, vigabatrin, lamotrigine, gabapentin, tiagabine, levetiracetam and desglycinyl‐remacemide were found to have no effect on GS activity.</jats:p>\n</jats:list-item>\n<jats:list-item>\n<jats:p>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.</jats:p>\n</jats:list-item>\n</jats:list>\n</jats:p><jats:p><jats:italic>British Journal of Pharmacology</jats:italic> (1999) <jats:bold>126</jats:bold>, 1634–1638; doi:<jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038/sj.bjp.0702472\">10.1038/sj.bjp.0702472</jats:ext-link></jats:p>","journal":"British Journal of Pharmacology","year":1999,"id":677721,"datarank":0.5742962094733643,"base_score":3.828641396489095,"endowment":3.828641396489095,"self_citation_contribution":0.5742962094733643,"citation_network_contribution":0.0,"self_endowment_contribution":0.5742962094733643,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":45,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1770772,"name":"Graeme J Sills","orcid":null,"position":1,"is_corresponding":false},{"id":149830,"name":"Gerard Forrest","orcid":null,"position":2,"is_corresponding":false},{"id":1770774,"name":"George G Thompson","orcid":null,"position":3,"is_corresponding":false},{"id":155060,"name":"Martin J Brodie","orcid":null,"position":4,"is_corresponding":false},{"id":1770770,"name":"Caroline M Fraser","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Effects of anti‐epileptic drugs on glutamine synthetase activity in mouse brain","abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item>\n<jats:p>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.</jats:p>\n</jats:list-item>\n<jats:list-item>\n<jats:p>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.</jats:p>\n</jats:list-item>\n<jats:list-item>\n<jats:p>Four hours after the final dose, animals were sacrificed and the brains removed for analysis of GS activity.</jats:p>\n</jats:list-item>\n<jats:list-item>\n<jats:p>Both single and repeated doses of phenytoin and carbamazepine were found to reduce enzyme activity (<jats:italic>P</jats:italic>&lt;0.05).</jats:p>\n</jats:list-item>\n<jats:list-item>\n<jats:p>Single doses of phenobarbitone, felbamate and topiramate were without effect, however repeated administration of these drugs dose‐dependently reduced GS activity (<jats:italic>P</jats:italic>&lt;0.05).</jats:p>\n</jats:list-item>\n<jats:list-item>\n<jats:p>Single and repeated doses of sodium valproate, vigabatrin, lamotrigine, gabapentin, tiagabine, levetiracetam and desglycinyl‐remacemide were found to have no effect on GS activity.</jats:p>\n</jats:list-item>\n<jats:list-item>\n<jats:p>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.</jats:p>\n</jats:list-item>\n</jats:list>\n</jats:p><jats:p><jats:italic>British Journal of Pharmacology</jats:italic> (1999) <jats:bold>126</jats:bold>, 1634–1638; doi:<jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038/sj.bjp.0702472\">10.1038/sj.bjp.0702472</jats:ext-link></jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"10323596","pmcid":"PMC1565942","openalex_id":null,"authors":[],"funders":[{"funder_name":"Wellcome Trust","grant_id":"","title":null}],"total_grants":1,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":null,"license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1038%2Fsj.bjp.0702472","host_type":"publisher"},{"url":"https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1038/sj.bjp.0702472","host_type":"publisher"}],"fields_of_study":[],"mesh_terms":["Brain","Animals","Mice, Inbred ICR","Mice","Ammonia","Glutamate-Ammonia Ligase","Anticonvulsants","Dose-Response Relationship, Drug","Male"],"keywords":[],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-17T04:28:06.309957Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}