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Topiramate selectively protects against seizures induced by ATPA, a GluR5 kainate receptor agonist.
Neuropharmacology. 2004 Jun; 46(8):1097-1104.N

Abstract

Although the mechanism of action of topiramate is not fully understood, its anticonvulsant properties may result, at least in part, from an interaction with AMPA/kainate receptors. We have recently shown that topiramate selectively inhibits postsynaptic responses mediated by GluR5 kainate receptors. To determine if this action of topiramate is relevant to the anticonvulsant effects of the drug in vivo, we determined the protective activity of topiramate against seizures induced by intravenous infusion of various ionotropic glutamate receptor agonists in mice. Topiramate (25-100 mg/kg, i.p.) produced a dose-dependent elevation in the threshold for clonic seizures induced by infusion of ATPA, a selective agonist of GluR5 kainate receptors. Topiramate was less effective in protecting against clonic seizures induced by kainate, a mixed agonist of AMPA and kainate receptors. Topiramate did not affect clonic seizures induced by AMPA or NMDA. In contrast, the thresholds for tonic seizures induced by higher doses of these various glutamate receptor agonists were all elevated by topiramate. Unlike topiramate, carbamazepine elevated the threshold for AMPA- but not ATPA-induced clonic seizures. Our results are consistent with the possibility that the effects of topiramate on clonic seizure activity are due to functional blockade of GluR5 kainate receptors. Protection from tonic seizures may be mediated by other actions of the drug. Together with our in vitro cellular electrophysiological results, the present observations strongly support a unique mechanism of action of topiramate, which involves GluR5 kainate receptors.

Authors+Show Affiliations

Epilepsy Research Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.Epilepsy Research Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.Epilepsy Research Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: michael.rogawski@nih.gov.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32585782

Citation

Kaminski, Rafal M., et al. "Topiramate Selectively Protects Against Seizures Induced By ATPA, a GluR5 Kainate Receptor Agonist." Neuropharmacology, vol. 46, no. 8, 2004, pp. 1097-1104.
Kaminski RM, Banerjee M, Rogawski MA. Topiramate selectively protects against seizures induced by ATPA, a GluR5 kainate receptor agonist. Neuropharmacology. 2004;46(8):1097-1104.
Kaminski, R. M., Banerjee, M., & Rogawski, M. A. (2004). Topiramate selectively protects against seizures induced by ATPA, a GluR5 kainate receptor agonist. Neuropharmacology, 46(8), 1097-1104. https://doi.org/10.1016/j.neuropharm.2004.02.010
Kaminski RM, Banerjee M, Rogawski MA. Topiramate Selectively Protects Against Seizures Induced By ATPA, a GluR5 Kainate Receptor Agonist. Neuropharmacology. 2004;46(8):1097-1104. PubMed PMID: 32585782.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Topiramate selectively protects against seizures induced by ATPA, a GluR5 kainate receptor agonist. AU - Kaminski,Rafal M, AU - Banerjee,Madhumita, AU - Rogawski,Michael A, Y1 - 2004/04/09/ PY - 2003/09/04/received PY - 2004/01/14/revised PY - 2004/02/03/accepted PY - 2020/6/27/entrez PY - 2004/6/1/pubmed PY - 2004/6/1/medline KW - AMPA KW - Carbamazepine KW - GluR5 KW - Kainate KW - Mouse KW - NMDA KW - Seizure KW - Topiramate SP - 1097 EP - 1104 JF - Neuropharmacology JO - Neuropharmacology VL - 46 IS - 8 N2 - Although the mechanism of action of topiramate is not fully understood, its anticonvulsant properties may result, at least in part, from an interaction with AMPA/kainate receptors. We have recently shown that topiramate selectively inhibits postsynaptic responses mediated by GluR5 kainate receptors. To determine if this action of topiramate is relevant to the anticonvulsant effects of the drug in vivo, we determined the protective activity of topiramate against seizures induced by intravenous infusion of various ionotropic glutamate receptor agonists in mice. Topiramate (25-100 mg/kg, i.p.) produced a dose-dependent elevation in the threshold for clonic seizures induced by infusion of ATPA, a selective agonist of GluR5 kainate receptors. Topiramate was less effective in protecting against clonic seizures induced by kainate, a mixed agonist of AMPA and kainate receptors. Topiramate did not affect clonic seizures induced by AMPA or NMDA. In contrast, the thresholds for tonic seizures induced by higher doses of these various glutamate receptor agonists were all elevated by topiramate. Unlike topiramate, carbamazepine elevated the threshold for AMPA- but not ATPA-induced clonic seizures. Our results are consistent with the possibility that the effects of topiramate on clonic seizure activity are due to functional blockade of GluR5 kainate receptors. Protection from tonic seizures may be mediated by other actions of the drug. Together with our in vitro cellular electrophysiological results, the present observations strongly support a unique mechanism of action of topiramate, which involves GluR5 kainate receptors. SN - 1873-7064 UR - https://www.unboundmedicine.com/medline/citation/32585782/Topiramate_selectively_protects_against_seizures_induced_by_ATPA,_a_GluR5_kainate_receptor_agonist L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(04)00048-6 DB - PRIME DP - Unbound Medicine ER -
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