Biochem/Physiol Actions | Topiramate is an anticonvulsant indicated in the treatment of epilepsy and migraine. Topiramate enhances GABA-activated chloride channels. In addition, topiramate inhibits excitatory neurotransmission, through actions on kainate and AMPA receptors. There is evidence that topiramate has a specific effect on GluR5 kainate receptors. It is also an inhibitor of carbonic anhydrase, particular subtypes II and IV, but this action is weak and unlikely to be related to its anticonvulsant actions, but may account for the bad taste and the development of renal stones seen during treatment. Its possible effect as a mood stabilizer seems to occur before anticonvulsant qualities at lower dosages. Topiramate inhibits maximal electroshock and pentylenetetrazol-induced seizures as well as partial and secundarily generalized tonic-clonic seizures in the kindling model, findings predective of a broad spectrum of antiseizure activities clinically. Topiramate is a sulfamate-substituted monosaccharide with anticonvulsant property. Although the mechanism of action has not been fully elucidated, topiramate antagonizes kainate/AMPA subtype of the glutamate receptors, which are ligand-activated cation channels that mediate the fast component of excitatory postsynaptic currents in neurons of the central nervous system. This antagonistic action results in stabilizing hyper-excited neural membranes, inhibiting repetitive neuronal firing, and decreasing propagation of synaptic impulses, thereby impedes seizure occurrences. In addition, this agent augments gamma-aminobenzoic acid (GABA) activity and thereby attenuating GABAnergic inhibitory transmission. |
