Seizure activity in photosensitive baboons following antidepressant drugs and the role of serotoninergic mechanisms.
Laboratroy and clinical evidence indicates that tricyclic antidepressants lower seizure threshold and in high doses may induce generalised seizures. In baboons with photosensitive epilepsy (Papio papio) the effects of 2 tricyclic antidepressants (imipramine and chlorimipramine) and of maprotiline and Nomi fensine have been studied (i.v. dose range 1-20 mg/kg. Imipramine, chlorimipramine and maprotiline (10 mg/kg i.v.) lowered seizure threshold to a comparable extent, whereas Nomifensine (10 mg/kg i.v-) did not enhance myoclinic responses to photic stimulation. Generalised seizures were seen 15-30 min after imipramine or chlorimipramine (20 mg/kg), and these two drugs showed no difference in their epileptogenicity. Administration of 5-hydroxytryptophan (25 mg/kg i.v.) 90 min before chlorimipramine or imipramine (10 mg/kg) completely blocked the usual augmentation of photically-induced epileptic responses. It is concluded that enhancement of serotoninergic activity following blockade of 5-HT re-uptake within the brain is unlikely to be responsible for enhanced myoclonic responses and epileptogenic seizures seen after tricyclic antidepressants. Nomifensine is significantly less epileptogenic than imipramine or chlorimipramine.
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D002997:Clomipramine / Q000494:pharmacology; D004569:Electroencephalography; D000882:Haplorhini; D007099:Imipramine / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008376:Maprotiline / Q000494:pharmacology; D010215:Papio; D010775:Photic Stimulation; D012640:Seizures / Q000139:chemically induced* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors
D000928:Antidepressive Agents; D007546:Isoquinolines; D008376:Maprotiline; D012701:Serotonin; D006916:5-Hydroxytryptophan; D002997:Clomipramine; D007099:Imipramine