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Animal model studies application to human patients

From the Department of Medicine, Section of Neurology, Dartmouth Medical School, Lebanon, NH.

Address correspondence and reprint requests to Dr. Gregory L. Holmes, Department of Neurology, Dartmouth Medical School, One Medical Center Drive, HB 7999, Lebanon, NH 03756 Gregory.holmes{at}hitchcock.org

Animal models are used to identify potential new antiepileptic drugs (AEDs) and to study the effects of combining AEDs with different mechanisms of action. The models most commonly used to identify new AEDs are the maximal electroshock (MES) test, the subcutaneous pentylenetetrazol (PTZ) test, and the electrical kindling model. The MES test has been useful in identifying agents that block generalized tonic-clonic seizures by prolonging the inactivation of sodium channels. The PTZ model has proved to be a good predictor of clinical efficacy of generalized spike-wave epilepsies of the absence type, and agents that reduce the calcium flow through T-type calcium channels or that enhance chloride flow through GABA(A) receptors are effective in this model. Electrically or chemically induced kindling is a model of epileptogenesis and has been used to study the epileptogenic process and the molecules that interfere with this process. Many epilepsy patients who fail to achieve adequate seizure control with different monotherapy agents and are unsuitable for surgical management are given polytherapy. Animal models can be used to evaluate different combinations of AEDs before their use in humans. Initial studies have identified combinations associated with supra-additive anticonvulsant effects that may warrant further study.

This supplement was supported by an educational grant from Novartis Pharmaceuticals Corporation.

Disclosure: The author received grants from the sponsor for other research activities not reported in this research/article and received honoraria (personal compensation) from the sponsor during the course of this study.

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