A New Anticonvulsant Pregabalin: Preclinical Data

Abstract

A New Anticonvulsant Pregabalin: Preclinical Data

Pregabalin is a highly potent compound with a newly defined mechanism of action that is showing activity in a number of conditions, such as epilepsy, anxiety, neuropathic pain. Although it is a structural analog of δ-aminobutyric acid (GABA), it does not have a direct effect on GABAergic mechanisms. Pregabalin is a ligand for the “alpha-2-delta” subunit of “voltage-gated calcium channels”, that exhibits anticonvulsant, analgesic, and anxiolytic activity in animal models. After binding potently to the alpha-2-delta subunit of the calcium channels, it reduces depolarization-induced calcium influx and thereby reduces release of several excitatory neurotransmitters. Pregabalin shows anticonvulsant activity in many animal models, including electroshock-induced seizures, kindled seizures in rats, chemical convulsant-induced seizures and seizures in genetically susceptible animals. It also demonstrated antiallodynic and antihyperalgesic activities in various rodent models of neuropathic pain and anxiolytic effects in the studies with the standard rat elevated X-maze and conflict test models of anxiety. Pregabalin pharmacokinetics was dose proportional and pregabalin was not significantly metabolized. The drug has a high oral bioavailability. It does not bind to plasma proteins. It did not show significant in vitro effect on the activities of cytochrome P450 isozymes. This article will review preclinical data of pregabalin as an anticonvulsant, analgesic and anxiolytic.