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Opioids: Effects on seizure threshold

Opioids exert their pharmacological effects by binding to specific receptors within and outside the CNS. They can be full or partial agonists of the mu, delta, and kappa opioid receptors.


In humans, pharmacologic doses of PO and IV morphine have little to no effect on seizure threshold. High doses of IV morphine have been shown to exert pro- and anti-convulsant properties in animal models; however, these doses far exceed those used in the clinical setting.


Neurotoxicity from meperidine is well-documented in humans and manifests as tremors, myoclonus, and seizures. The neurotoxic effects of meperidine are largely attributed to high serum levels of it’s active metabolite, normeperidine, which has a half-life of 15-20h, (compared to 3-4h of its parent compound), in addition to decreased analgesic and pro-convulsant properties. Because of the long half-life of normeperidine, patients receiving scheduled doses of meperidine are at increased risk for seizures. The risk is greater with oral administration (owing to significant first-pass metabolism), although seizures and neurotoxicity have been documented with all routes of administration. Additionally, patients with renal disease and patients taking drugs that increase CYP450 activity (such as phenytoin) are at greater risk of seizure due to decreased excretion of normeperidine or increased metabolization into normeperidine, respectively.

Fentanyl (and it’s congeners)

Fentanyl and its congeners have not demonstrated pro- or anti-convulsant properties.


  1. Modica PA, Tempelhoff R, White PF. Pro- and anticonvulsant effects of anesthetics (Part I) Anesth Analg. 1990 Mar;70(3):303-15. PubMed Link