Effects of co-administration of a selective serotonin reuptake inhibitor 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 in the case of co-administration of a monoamine oxidase (MAO) inhibitor and a serotonin reuptake inhibitor (SSRI). The goal of the present study was to investigate the effects of acute administration of MAO inhibitors and subchronic administration of fluvoxamine on 5-HT-related behaviors (head shaking and 5-HT syndrome) in rats treated with 5-hydroxytryptophan (5-HTP). Administration of the non-selective MAO inhibitor, pargyline, and the selective MAO-A inhibitor, clorgyline, resulted in 5-HT syndrome in 5-HTP-treated rats, and subchronic co-administration of fluvoxamine intensified the syndrome. However, administration of the selective MAO-B inhibitor, selegiline, did not induce 5-HT syndrome with or without subchronic fluvoxamine co-administration. These data suggest that non-selective MAO and selective MAO-A inhibitors can induce 5-HT syndrome in humans when co-administered with SSRI. Further, the risk of 5-HT syndrome may be lower with the selective MAO-B inhibitor, selegiline.
Department of Psychiatry, Hokkaido University Graduate School of Medicine, North 15, West 7, Sapporo 060-8638, Japan. psyizumi@med.hokudai.ac.jp
Takeshi
T
Izumi
Nobuyuki
N
Iwamoto
Yuji
Y
Kitaichi
Akiko
A
Kato
Takeshi
T
Inoue
Tsukasa
T
Koyama
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D003010:Clorgyline / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D016666:Fluvoxamine / Q000633:toxicity; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000633:toxicity*; D009043:Motor Activity / Q000187:drug effects; D010293:Pargyline / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012642:Selegiline / Q000633:toxicity; D012701:Serotonin; D020230:Serotonin Syndrome / Q000209:etiology* / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000633:toxicity*
D003010:Clorgyline; D016666:Fluvoxamine; D008996:Monoamine Oxidase Inhibitors; D010293:Pargyline; D012642:Selegiline; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors