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In monotherapy clinical trials of topiramate 50 to 200 mg/day for the prophylaxis of migraines, the following CNS effects occurred more frequently with topiramate than placebo: paresthesias (35% to 51% vs

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The machinery it drives inside the cell maxes out long before the receptor itself fills, so the effect can run flat-out while occupancy is still tiny (the spare-receptor effect). Retatrutide runs on this