The role of serotonin in the pathophysiology of myoclonic seizures associated with acute imipramine toxicity

Article abstract Seizures are a well-known manifestation of imipramine toxicity, but the pathophysiology of these seizures is unknown. Since myoclonic seizures can be generated in guinea pigs with 5-hydroxytryptophan, the precursor of serotonin, and since imipramine has been observed to decrease the reuptake to serotonin in the brain, an attempt was made to potentiate 5-hydroxytryptophan-induced myoclonus in guinea pigs with imipramine. Subthreshold doses of 5-hydroxytryptophan together with 35 mg per kilogram of imiparmine consistently led ?o myoclonic seizures in the animals. Antagonists of norepinephrine, dopamine, and acetylcholine all failed to block the potentiation of 5-hydroxytryptophan-induced seizures with imipramine. These results are consistent with the hypothesis that imiprarnine acts via serotonergic mechanisms in the brain to produce myoclonic seizures.