The mechanism of action of noradrenergic and specific serotonergic antidepressants

Depression is associated with reduced levels of monoamines in the brain. Noradrenergic and specific serotonergic antidepressants (NaSSAs), such as mirtazapine, have a dual mechanism of action that increases the concentration of 5-HT and noradrenaline in the synaptic cleft to within the normal range. NaSSAs bind to and inhibit both noradrenaline a2-autoreceptors and noradrenaline a2-heteroeceptors. This action prevents the negative feedback effect of synaptic noradrenaline on 5-HT and noradrenaline neurotransmission, and neurotransmission sustained. NaSSAs also block 5-HT2 and 5-HT3 receptors on the post-synaptic membrane, which causes enhanced 5-HT1 mediated neurotransmission.

  1. J Clin Psychiatry 1996;57(Suppl 4):19–25.
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