The antidepressant activity of mirtazapine, an NaSSA agent, is thought to result
from a combination of noradrenergic and serotonergic effects, with the latter specifically
involving enhancement of serotonin 5-HT1 receptor-mediated effects. It acts
as an antagonist at central a2-adrenergic autoreceptors and heteroreceptors, and
postsynaptic 5-HT2 and 5-HT3 receptors. Mirtazapine has low affinity for central
and peripheral dopaminergic receptors, but is a potent antagonist of histamine H1
receptors and a moderate antagonist at muscarinic receptors. Mirtazapine improves
sleep efficiency and continuity, and does not suppress rapid eye movement sleep.
Mirtazapine is absorbed rapidly after oral administration, with peak plasma
concentrations achieved within 2 hours. Food has no clinically relevant effect on
absorption. Mirtazapine displays linear pharmacokinetics over the therapeutic
dosage range, and steady state is reached after »5 days. Mirtazapine is extensively
metabolized, principally via cytochrome P450 (CYP) isoenzymes CYP3A4,
CYP2D6 and CYP1A2. The elimination half-life of mirtazapine is 20–40 hours.
Mirtazapine is a racemate and the enantiomers display differing pharmacokinetic
and pharmacodynamic properties; both enantiomers contribute to the pharmacodynamic
effects of mirtazapine.
The antidepressant activity of mirtazapine, an NaSSA agent, is thought to result
from a combination of noradrenergic and serotonergic effects, with the latter specifically
involving enhancement of serotonin 5-HT1 receptor-mediated effects. It acts
as an antagonist at central a2-adrenergic autoreceptors and heteroreceptors, and
postsynaptic 5-HT2 and 5-HT3 receptors. Mirtazapine has low affinity for central
and peripheral dopaminergic receptors, but is a potent antagonist of histamine H1
receptors and a moderate antagonist at muscarinic receptors. Mirtazapine improves
sleep efficiency and continuity, and does not suppress rapid eye movement sleep.
Mirtazapine is absorbed rapidly after oral administration, with peak plasma
concentrations achieved within 2 hours. Food has no clinically relevant effect on
absorption. Mirtazapine displays linear pharmacokinetics over the therapeutic
dosage range, and steady state is reached after »5 days. Mirtazapine is extensively
metabolized, principally via cytochrome P450 (CYP) isoenzymes CYP3A4,
CYP2D6 and CYP1A2. The elimination half-life of mirtazapine is 20–40 hours.
Mirtazapine is a racemate and the enantiomers display differing pharmacokinetic
and pharmacodynamic properties; both enantiomers contribute to the pharmacodynamic
effects of mirtazapine.
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