Effect of nomifensine on brain amines and epilepsy in photosensitive baboons.
1. The literature, both clinical and experimental, suggests that tricyclic antidepressants are potentially epileptogenic. Using the experimental model of epilepsy provided by the photosensitive baboon, Papio papio, the epileptic potential of four antidepressant drugs, two of which are tricyclic, has been assessed. The drugs used were imipramine 1, 10 and 20 mg/kg, chlorimipramine 1, 10 and 20 mg/kg, maprotiline 1 and 10 mg/kg and nomifensine 10 and 20 mg/kg. In a second series of experiments the 5-hydroxytryptamine (5-HT) precursor 5-hydroxytryptophan (5-HTP) 10 and 25 mg/kg has been administered before administration of imipramine 10 mg/kg and chlorimipramine 10 mg/kg. 2. The results of the experiments indicate that at 10 mg/kg imipramine, chlorimipramine and maprotiline all induce seizures and lower the seizure threshold. In contrast nomifensine at this dose did not alter the seizure threshold. 5-HTP 25 mg/kg administered before the antidepressants, abolished seizures. These results are discussed in the light of other experiments which have attempted to explain the pathophysiology of epileptic seizures following antidepressants, and it is concluded that dopaminergic mechanisms are probably responsible for the differing effect noted with nomifensine.
D000588:Amines / Q000378:metabolism*; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002997:Clomipramine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007099:Imipramine / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology*; D008376:Maprotiline / Q000494:pharmacology; D009627:Nomifensine / Q000494:pharmacology*; D010215:Papio; D010775:Photic Stimulation; D012640:Seizures / Q000139:chemically induced* / Q000517:prevention & control
D000588:Amines; D007546:Isoquinolines; D009627:Nomifensine; D008376:Maprotiline; D002997:Clomipramine; D007099:Imipramine