The effects of mirtazapine on central noradrenergic and serotonergic neurotransmission

被引:152
作者
deBoer, T
机构
[1] Department of Neuropharmacology, Scientific Development Group, Oss, 5340 BH, N.V. Organon
关键词
mirtazapine; alpha(2)-adrenoceptors; serotonin release; antidepressant;
D O I
10.1097/00004850-199512004-00004
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Mirtazapine is a new antidepressant with a unique mode of action: it preferentially blocks the noradrenergic alpha(2)-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).
引用
收藏
页码:19 / 23
页数:5
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