The pharmacologic profile of mirtazapine.
Mirtazapine (Org 3770) is a new antidepressant with prominent alpha 2-adrenergic auto- and heteroreceptor antagonistic properties and no effect on monoamine reuptake. Mirtazapine increases noradrenergic and serotonergic transmission, as measured by on-line microdialysis and by enhancement of noradrenergic locus ceruleus and serotonergic raphe nucleus cell firing. Mirtazapine has a low affinity for 5-HT1A receptors but shows 5-HT1A-agonistic-like effects in a conditioned taste aversion test and by causing lower lip retraction in rats. Mirtazapine therefore causes enhancement of 5-HT1-mediated transmission. Other studies show that both 5-HT2 and 5-HT3 receptors are specifically blocked. The enhancement of both noradrenergic and serotonergic transmission probably underlies the therapeutic activity of mirtazapine. Blockade of 5-HT2 and 5-HT3 receptors possibly prevents side effects associated with nonselective 5-HT activation and may also contribute to the anxiolytic and sleep-improving properties of mirtazapine.
de Boer
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Neuropharmacology Department, Scientific Development Group, N.V. Organon, The Netherlands.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology* / Q000627:therapeutic use; D017660:Autoreceptors / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D003866:Depressive Disorder / Q000188:drug therapy*; D004146:Dioxanes / Q000494:pharmacology / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D006801:Humans; D019329:Idazoxan; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use; D008803:Mianserin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000078785:Mirtazapine; D051381:Rats; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D000929:Antidepressive Agents, Tricyclic; D017660:Autoreceptors; D004146:Dioxanes; D007093:Imidazoles; D017981:Receptors, Neurotransmitter; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D008803:Mianserin; D000078785:Mirtazapine; D019329:Idazoxan