COMPARISON OF THE PHARMACOLOGICAL AND BIOCHEMICAL PROFILES OF VALPROIC ACID (VPA) AND ITS CEREBRAL METABOLITE (2-EN-VPA) AFTER ORAL-ADMINISTRATION IN MICE
- 1 January 1985
- journal article
- research article
- Vol. 7 (2) , 83-86
Abstract
The pharmacological and biochemical profiles of valproate (VPA) and its cerebral metabolite (2-en-VPA [trans-2-propyl-2-pentenoic acid] were compared in order to determine the potential therapeutic value of the latter. After oral administration, 2-en-VPA was approximately 1/2 as potent as VPA in a number of chemical seizure models (pentylenetetrazol, B-mercaptopropionic acid, bicuculline and picrotoxinin), but more potent in tests of sedative activity (rotarod and loss of righting reflex). Whereas VPA possessed anxiolytic activity in mice, 2-en-VPA appeared to be inactive. The anticonvulsant activity of 2-en-VPA was shorter-lasting than that of VPA. The activity of 4 mmol/kg 2-en-VPA lasted less than 2 h, while the same dose of VPA provided protection for over 5 h. Both molecules increased brain GABA content to a similar extent, but again the action of 2-en-VPA was short-lasting. The low potency, poor ratio of sedative:anticonvulsant activity, and short-lived action of 2-en-VPA suggest that the molecule is poorly adapted for use as an antiepileptic agent.This publication has 4 references indexed in Scilit:
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