Fig. 1

Potential mechanisms of action for the anti-migraine effect of topiramate. Topiramate is proposed to act via inhibition of nociceptive neuronal firing in the trigeminocervical complex in animal models [12]. Firstly, excitatory neurotransmission is reduced via downregulation of postsynaptic AMPA/kainate receptors and Na + channels [13,14,15]. Moreover, topiramate enhances GABA_A receptor activity, thereby promoting inhibitory GABAergic neurotransmission [14, 15]. By inhibition of voltage-gated Ca²⁺ channels, topiramate may prevent the release of vasoactive neuropeptides including CGRP [16]. Collectively, by altering activation and sensitization of neurons, these mechanisms could prevent migraine attacks and cortical spreading depression [8, 17]