According to the website of the manufacturer, Topamax is hypothesized to function by keeping excitable nerve cells in the brain “calm.” It does this via modulation of charged particle inflow and outflow.
In other words, when a person takes Topamax and the topiramate chemical crosses the blood-brain-barrier (BBB), it essentially relaxes or downregulates overexcitability of neurons, thereby preventing the series of neurologic events that triggers a migraine attack.
After its synthesis, preliminary evaluation lead researchers to speculate that Topamax may prevent seizures.
As a result of safety and efficacy in human clinical trials, Topamax received FDA approval in 1996 for the treatment of partial seizures in adults; thereafter it was also approved for usage among pediatrics.
Although Topamax is still frequently utilized as a seizure preventative, and is sometimes administered for psychiatric conditions (e.g.
bipolar disorder) – it remains most commonly prescribed as a migraine prophylactic.
This reduces dendritic excitability and possibly increases the stimulatory threshold required to provoke a migraine.
It is known that mutations in CACNA1A, a gene that encodes for the alpha-1 subunit of Ca V2.1 (P/Q-type) channels causes familial hemiplegic migraine type 1 (FHM1).
In 2011, researchers Andreou and Goadsby published a study assessing the effect of Topamax on trigeminovascular activity in the trigeminocervical complex (TCC) and ventroposteromedial thalamic nucleus (VPM).Knowing that the mechanisms of anticonvulsants may be useful for the prevention of migraines resulted in some physicians prescribing Topamax (from 1996 to 2004) as an off-label migraine prophylactic.In 2004, Topamax had met clinical trial endpoints and received official FDA approval for the prophylaxis of migraine.Therefore, users of Topamax may not only experience fewer migraines from its modulation of kainate receptors, but also less migraine-related pain.: Another way by which Topamax may prevent migraines is via reducing activity of L-type voltage-gated calcium channels.It is understood that L-type calcium channels play a role in modulating excitability of dendrites.It is thought that kainate receptor antagonism induced by Topamax altered the trigeminovascular activity within the trigeminothalamic pathway, possibly decreasing the release of neurochemicals and neuropeptides such as: substance P, CGRP, and gastrin-releasing peptide.In addition to preventing migraine attacks by antagonizing kainate receptors, this mechanism may also reduce migraine-related pain due to the fact that kainate receptors can be found in the central pain neuraxis.Topamax (Topiramate) is an anticonvulsant agent discovered in 1979 by Bruce Maryanoff and Joseph Gardocki while working for Mc Neil Pharmaceutical (a subsidiary of Johnson & Johnson).When compared to other anticonvulsant agents, Topamax is regarded as unique in that it is pharmacologically classified as a sulfamate-substituted monosaccharide derivative, indicating that its chemical structure is similar to that of fructose.This finding suggests that voltage-gated calcium currents may play a role in the pathogenesis of migraines (for certain individuals).Although Topamax does not appear to modulate the P/Q-type voltage-gated calcium channels, its modulation of the L-type channels may be enough to reverse some calcium channel abnormalities exhibited among migraine patients.Unlike other migraine prophylactics, Topamax is regarded as well-tolerated with few unwanted adverse effects.Moreover, Topamax has robust, “Level A” evidence to support its clinical usage as a first-line agent the prevention of migraine.While not all voltage-gated sodium channel inhibitors are effective migraine prophylactics (e.g. That said, other complementary mechanisms may be necessary for clinically effective prophylaxis of migraines.: An important mechanism by which Topamax may prevent migraines is via inhibition of glutamate receptors.