title: Mirtazapine abolishes hyperthermia in an animal model of serotonin syndrome.
abstract: Serotonin (5-HT) syndrome is a potentially fatal condition associated with various combinations of serotonergic drugs. Hyperthermia is the most serious symptom of this syndrome. Hyperthermia in 5-HT syndrome is reportedly the result of activation of 5-HT(2A) receptors. Mirtazapine is a novel antidepressant and a potent 5-HT(2) receptor antagonistic. Although mirtazapine has been reported to cause 5-HT syndrome, the pharmacological profile of mirtazapine suggests that it improves hyperthermia in 5-HT syndrome. In the present study, we evaluated whether mirtazapine attenuates hyperthermia in a rat model of 5-HT syndrome. This model was induced by administration of tranylcypromine, a nonselective monoamine oxidase inhibitor, and fluoxetine, a selective serotonin reuptake inhibitor. Upon injection of these two drugs, the rectal temperature of the rats increased to over 40 degrees C. Pre- and post-administration of mirtazapine abolishes hyperthermia in this model of 5-HT syndrome. Post-administration of ritanserin, a 5-HT(2A) receptor antagonist, completely inhibited hyperthermia and pre-administration of WAY100635, a 5-HT(1A) receptor antagonist, significantly attenuated the ability of mirtazapine to abolish hyperthermia. The results of the present study suggest that mirtazapine inhibits hyperthermia in an animal model of 5-HT syndrome by blocking the activation of 5-HT(2A) receptors, and that it partly inhibits hyperthermia by activating the 5-HT(1A) receptors. The present study indicates that mirtazapine is unlikely to cause 5-HT syndrome and may be a useful drug for treating this condition.
authors.affiliation: Department of Psychiatry, Jichi Medical University, Yakushiji, Shimotsuke-shi, Tochigi-Ken 329-0498, Japan. kazs@jichi.ac.jp
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Shioda
authors.forename: Koichi
authors.initials: K
authors.lastname: Nisijima
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Yoshino
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kato
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D004195:Disease Models, Animal; D005334:Fever / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000078785:Mirtazapine; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism; D012702:Serotonin Antagonists / Q000627:therapeutic use*; D020230:Serotonin Syndrome / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D044402:Receptor, Serotonin, 5-HT2A; D012702:Serotonin Antagonists; D044282:Receptor, Serotonin, 5-HT1A; D008803:Mianserin; D000078785:Mirtazapine