Effects of co-administration of antidepressants and monoamine oxidase inhibitors on 5-HT-related behavior in rats.
5-hydroxytryptamine (5-HT) syndrome is a dangerous condition of 5-HT excess that can occur during co-administration of a monoamine oxidase (MAO) inhibitor and an antidepressant. We investigated the effects of acute administration of MAO inhibitors and subchronic administration of tricyclic and heterocyclic antidepressants, and a serotonin-noradrenaline reuptake inhibitor (SNRI) on 5-HT syndrome in rats treated with 5-hydroxytryptophan (5-HTP). The irreversible and non-selective MAO inhibitor pargyline, and the reversible and selective MAO-A inhibitor clorgyline, produced increases in 5-HT syndrome in the 5-HTP-treated rats, while subchronic co-administration of imipramine partly intensified and partly attenuated the syndrome, whereas milnacipran only attenuated the syndrome. Co-administration of mianserin partly intensified and partly attenuated the syndrome but the attenuating effect was dominant. Administration of the irreversible and selective MAO-B inhibitor selegiline did not produce any increase in 5-HT syndrome in the 5-HTP-treated rats, compared with the saline control. These data suggest that non-selective MAO and selective MAO-A inhibitors can induce 5-HT syndrome in humans when co-administered with antidepressants. Furthermore, the risk of 5-HT syndrome may be lower with the selective MAO-B inhibitor selegiline.
Izumi
Takeshi
T
Department of Psychiatry, Hokkaido University Graduate School of Medicine, North 15, West 7, Sapporo 060-8638, Japan. psyizumi@med.hokudai.ac.jp
Iwamoto
Nobuyuki
N
Kitaichi
Yuji
Y
Kato
Akiko
A
Inoue
Takeshi
T
Koyama
Tsukasa
T
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D003521:Cyclopropanes / Q000494:pharmacology; D004347:Drug Interactions; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D008803:Mianserin / Q000494:pharmacology; D000078764:Milnacipran; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D020230:Serotonin Syndrome / Q000139:chemically induced*
D000928:Antidepressive Agents; D003521:Cyclopropanes; D008996:Monoamine Oxidase Inhibitors; D008803:Mianserin; D012701:Serotonin; D006916:5-Hydroxytryptophan; D000078764:Milnacipran; D007099:Imipramine