Mirtazapine abolishes hyperthermia in an animal model of serotonin syndrome.
Summary of "Mirtazapine abolishes hyperthermia in an animal model of serotonin syndrome."
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 2 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 WAY 100635, 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.
Affiliation
Department of Psychiatry, Jichi Medical University, Yakushiji Shimotsuke-shi, Tochigi-Ken, 329-0498, Japan.
Journal Details
This article was published in the following journal.
Name: Neuroscience letters
ISSN: 1872-7972
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20655983
- DOI: http://dx.doi.org/10.1016/j.neulet.2010.07.039
Medical and Biotech [MESH] Definitions
Serotonin Syndrome
An adverse drug interaction characterized by altered mental status, autonomic dysfunction, and neuromuscular abnormalities. It is most frequently caused by use of both serotonin reuptake inhibitors and monoamine oxidase inhibitors, leading to excess serotonin availability in the CNS at the serotonin 1A receptor.
Norfenfluramine
A FENFLURAMINE analog that inhibits serotonin uptake and may provoke release of serotonin. It is used as an appetite depressant and an experimental tool in animal studies.
Serotonin Antagonists
Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or serotonin agonists.
Models, Statistical
Statistical formulations or analyses which, when applied to data and found to fit the data, are then used to verify the assumptions and parameters used in the analysis. Examples of statistical models are the linear model, binomial model, polynomial model, two-parameter model, etc.
Serotonin 5-ht4 Receptor Antagonists
Drugs that bind to but do not activate SEROTONIN 5-HT4 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN RECEPTOR AGONISTS.
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