Paradoxical cerebral cortical hyperexcitability following flupirtine overdose.

We report the case of a patient with increased cerebral cortical excitability following intoxication with flupirtine, a centrally acting analgesic and antispastic drug. Typically, flupirtine exerts membrane stabilizing and hyperpolarizing effects through activation of neuronal G-protein regulated inwardly rectifying potassium channels (GIRK). Based on these properties, GIRK activators have been suggested as candidates for antiepileptic drug development. In contrast, our observation suggests that these substances may also display unexpected proconvulsant effects in vivo.