EEG effects of IV infusion of pentylenetetrazol in rats: A model for screening and classifying antiepileptic compounds |
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Authors: | Vincent Santucci Michèle Fournier Peter Keane Jacques Simiand Jean-Claude Michaud Michel Morre Kathleen Biziere |
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Affiliation: | (1) Groupe Sanofi, Centre de Recherches Clin-Midy, Rue du Prof. J. Blayac, F-34082 Montpellier Cedex, France;(2) Sanofi Recherche, 195 Route d'Espagne, F-31035 Toulouse Cedex, France |
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Abstract: | In order to validate a new animal model predictive of the profile of antiepileptic drugs, we studied the antagonism by standard antiepileptics of the EEG modifications induced by low-speed IV infusion of pentylenetetrazol (PTZ) in rats. The activity of the drugs was measured by their effects on temporal characteristics of the PTZ-induced EEG paroxysms. Most compounds had moderate to potent anti-PTZ effects, as shown by the changes in the EEG temporal parameters. However, these effects depended on the drugs and doses. Cluster analysis showed that drugs and doses which evoked similar changes were closely related and were included in separate clusters with respect to one another. In particular, the present results showed that benzodiazepines and antiepileptics cluster differently in their effects. Thus, this model could be a useful tool for assessing new antiepileptic drugs. |
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Keywords: | EEG Pentylenetetrazol Antiepileptic drugs Cluster analysis Rat |
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