Indirect α1 adrenoceptor-mediated enhancement of serotonin cell firing and direct blockade of inhibitory α2 heteroreceptors located on serotonin terminals are held responsible for the increase in extracellular serotonin. Because of this, mirtazapine has been said to be a functional "indirect agonist" of the 5-HT1A receptor. Increased activation of the central 5-HT1A receptor is thought to be a major mediator of efficacy of most antidepressant drugs. 5-HT2 receptor
Antagonism of the 5-HT2 subfamily of receptors and inverse agonism of the 5-HT2C receptor appears to be in part responsible for mirtazapines efficacy in the treatment of depressive states. Mirtazapine increases dopamine release in the prefrontal cortex. Accordingly, it was shown that by blocking the α2-adrenergic receptors and 5-HT2C receptors mirtazapine disinhibited dopamine and norepinephrine activity in these areas in rats. In addition, mirtazapines antagonism of 5-HT2A receptors has beneficial effects on anxiety, sleep and appetite, as well as sexual function regarding the latter receptor. Mirtazapine has been shown to lower drug seeking behaviour (more specifically to methamphetamine) in various human and animal studies. It is also being investigated in substance abuse disorders to reduce withdrawal effects and improve remission rates.Mirtazapine significantly improves pre-existing symptoms of nausea, vomiting, diarrhea, and irritable bowel syndrome in affected individuals. Mirtazapine may be used as an inexpensive antiemetic alternative to Ondansetron. In conjunction with substance abuse counseling, mirtazapine has been investigated for the purpose of reducing methamphetamine use in dependent individuals with success.
: 430

Chemistry
Mirtazapine is a tetracyclic piperazinoazepine; mianserin was developed by the same team of organic chemists and mirtazapine differs from it via addition of a nitrogen atom in one of the rings. : 429  It is a racemic mixture of enantiomers. The (S)-(+)-enantiomer is known as esmirtazapine. Analogues of mirtazapine include mianserin, setiptiline, and aptazapine. Synthesis
A chemical synthesis of mirtazapine has been published. The first step of synthesis is a condensation reaction between the molecule 2-chloro 3-cyanopyridine and the molecule 1-methyl-3-phenylpiperazine. History
Mirtazapine was first synthesized at Organon and published in 1989, was first approved for use in major depressive disorder in the Netherlands in 1994, and was introduced in the United States in 1996 under the brand name Remeron. : 429

Society and culture
Generic names
Mirtazapine is the English and French generic name of the drug and its INN, USAN, USP, BAN, DCF, and JAN. Its generic name in Spanish, Italian and Portuguese is mirtazapina and in German and Swedish is Mirtazapin.