For the treatment of major depressive disorder.
Mirtazapine acts as an antagonist at central pre-synaptic alpha(2)-receptors, inhibiting negative feedback to the presynaptic nerve and causing an increase in NE release. Blockade of heteroreceptors, alpha(2)-receptors contained in serotenergic neurons, enhances the release of 5-HT, increasing the interactions between 5-HT and 5-HT<sub>1</sub> receptors and contributing to the anxiolytic effects of mirtazapine. Mirtazapine also acts as a weak antagonist at 5-HT<sub>1</sub> receptors and as a potent antagonist at 5-HT<sub>2</sub> (particularly subtypes 2A and 2C) and 5-HT<sub>3</sub> receptors. Blockade of these receptors may explain the lower incidence of adverse effects such as anxiety, insomnia, and nausea. Mirtazapine also exhibits significant antagonism at H1-receptors, resulting in sedation. Mirtazapine has no effects on the reuptake of either NE or 5-HT and has only minimal activity at dopaminergic and muscarinic receptors.
Symptoms of overdose include disorientation, drowsiness, impaired memory, and tachycardia. LD50 is 600-720mg/kg (oral, mice) and 320-490mg/kg (oral, rat) [PMID: 10333982]
Rapid and complete, but, due to first-pass metabolism, absolute bioavailability is 50%.
20-40 hours
This drug is known to be substantially excreted by the kidney (75%).