The effects of mirtazapine on central noradrenergic and serotonergic neurotransmission.
Mirtazapine is a new antidepressant with a unique mode of action: it preferentially blocks the noradrenergic alpha2-auto- and heteroreceptors held responsible for controlling noradrenaline and serotonin release. In addition, mirtazapine has a low affinity for serotonin (5-HT)1A receptors but potently blocks 5-HT2 and 5-HT3 receptors. It increases serotonergic cell-firing in the dorsal raphe and 5-HT release in the hippocampus as measured by microdialysis. These effects are explained by noradrenergic enhancement of 5-HT cell-firing and blockade of noradrenaline-mediated inhibition of hippocampal 5-HT release. Because mirtazapine blocks 5-HT2 and 5-HT3 receptors, only 5-HT1-mediated transmission is enhanced. The noradrenergic activation and the consequent indirect enhancement of serotonergic transmission most probably underlie the marked therapeutic activity of mirtazapine. The blockade of 5-HT2 and 5-HT3 receptors prevents development of the side effects associated with non-selective 5-HT activation and may contribute to the anxiolytic and sleep-improving properties of this new compound. Therefore mirtazapine can be described as a noradrenergic and specific serotonergic antidepressant (NaSSA).
de Boer
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Department of Neuropharmacology, Scientific Development Group, N.V. Organon, The Netherlands.
D058669:Adrenergic alpha-2 Receptor Antagonists; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects / Q000627:therapeutic use*; D001143:Arousal / Q000187:drug effects / Q000502:physiology; D017660:Autoreceptors / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D003866:Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D006634:Histamine H1 Antagonists / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008803:Mianserin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000078785:Mirtazapine; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects* / Q000502:physiology; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology
D058669:Adrenergic alpha-2 Receptor Antagonists; D000929:Antidepressive Agents, Tricyclic; D017660:Autoreceptors; D006634:Histamine H1 Antagonists; D011941:Receptors, Adrenergic; D018341:Receptors, Adrenergic, alpha-2; D011985:Receptors, Serotonin; D008803:Mianserin; D000078785:Mirtazapine