Mechanism of Action

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How is topiramate believed to help prevent migraine?

Watch this video to learn how topiramate is believed to act on the brain to prevent migraine. Although the exact mechanism by which topiramate affects migraine is unknown, it is believed to act in the brain to modulate multiple neuronal targets, which may suppress the overall neural hyperexcitability that may increase an individual’s susceptibility to migraine attacks.1-3


Topiramate is believed to modulate multiple neuronal targets:

  • In the neurons of the trigeminovascular system, topiramate may act presynaptically to inhibit the function of sodium channels, resulting in decreased likelihood of action-potential propagation. This may help prevent the release of neurotransmitters and peptides that are implicated in migraine attacks.2
  • In addition to topiramate’s indirect effect on calcium channels through its effect on action-potential propagation, topiramate may inhibit the activation of voltage-gated calcium channels at the presynaptic nerve terminal, blocking the release of multiple neurotransmitters and peptides, including glutamate and CGRP, into the synapse. This may help prevent the initiation of migraine by impeding the propagation of downstream pain signaling.2
  • Topiramate also may act post synaptically, by inhibiting the activity of kainite and AMPA subtypes of glutamate receptors, and by augmenting the influx of chloride through GABA-A receptors, which may further reduce neurotransmission and downstream pain signaling.2,4

In complex multifactorial disorders like migraine, topiramate’s multimodal mechanism of action targeting multiple neuronal targets has been hypothesized as a contributor to its efficacy as a migraine-preventive medication.1,2,5








Please refer to the full Prescribing Information and Medication Guide for additional important information on Trokendi XR.

Trokendi XR (topiramate) extended-release capsules



  1. Trokendi XR [package insert]. Rockville, MD: Supernus Pharmaceuticals, Inc; 2018.
  2. Silberstein SD. Topiramate in migraine prevention: a 2016 perspective. Headache. 2017;57(1):165-178.
  3. Ruiz L, Ferrandi D. Topiramate in migraine progression. J Headache Pain. 2009;10(6):419-422.
  4. White HS, Brown D, Woodhead JH, et al. Topiramate enhances GABA-mediated chloride flux and GABA-evoked chloride currents in murine brain neurons and increases seizure threshold. Epilepsy Res. 1997;28:167-179.
  5. Charles A. The pathophysiology of migraine: implications for clinical management. Lancet Neurol. 2018;17:174-182.
  6. Data on file. Supernus Pharmaceuticals, Inc., Rockville, MD.