Pharmacodynamic interaction studies with topiramate in the pentylenetetrazol and maximal electroshock seizure models

Sills, G. J., Butler, E., Thompson, G. G. and Brodie, M. J. (2004) Pharmacodynamic interaction studies with topiramate in the pentylenetetrazol and maximal electroshock seizure models. Seizure, 13(5), pp. 287-295. (doi:10.1016/S1059-1311(03)00185-7) (PMID:15158698)

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Abstract

There is emerging evidence to support the efficacy of some antiepileptic drug (AED) combinations in refractory epilepsy. Definitive clinical studies are, however, difficult to perform. Experimental seizure models can be employed to identify potentially useful combinations for subsequent clinical evaluation. We have investigated the anticonvulsant effects of topiramate (TPM) in combination with 13 other AEDs in the pentylenetetrazol (PTZ) and maximal electroshock (MES) seizure models. Single drugs and combinations were administered by intraperitoneal injection and anticonvulsant effects determined at 1-hour post-dosing. TPM was without significant effect in the PTZ test. In contrast, phenobarbital, primidone, ethosuximide, sodium valproate, felbamate and tiagabine all increased the latency to the first generalised seizure. Combinations of TPM and active adjunctive drug were universally effective. Combinations of TPM with clobazam, lamotrigine and levetiracetam were also anticonvulsant, despite the inactivity of the constituent compounds when administered alone. TPM reduced the incidence of MES-induced seizures in a dose-dependent manner, as did phenobarbital, phenytoin, primidone, carbamazepine, sodium valproate, clobazam, lamotrigine, felbamate and tiagabine. All combination treatments were similarly effective. These findings suggest that combinations of TPM with lamotrigine and levetiracetam may demonstrate anticonvulsant synergism and merit further investigation in additional model systems and with recourse to more quantitative mathematical analysis.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Brodie, Professor Martin and Butler, Mrs Elaine and Sills, Dr Graeme
Authors: Sills, G. J., Butler, E., Thompson, G. G., and Brodie, M. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > School of Life Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Seizure
Publisher:Elsevier
ISSN:1059-1311
ISSN (Online):1532-2688

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