QuickView for Mirtazapine (compound)

Summary
General Info

PubChem

PubChem Compound 3085218

Name:	mirtazapine
PubChem Compound ID:	3085218
Molecular formula:	C₁₇H₁₉N₃
Molecular weight:	265.353 g/mol
Synonyms:	Tocris-2018; 61337-87-9; NCGC00025346-01; (S)-1,2,3,4,10,14b-Hexahydro-2-methylpyrazino(2,1-a)pyrido(2,3-c)(2)benzazepine; EINECS 262-714-0

DrugBank

Identification

Name:	mirtazapine
Name (isomeric):	DB00370
Drug Type:	small molecule
Synonyms:	Mirtazapinum [INN-Latin]; Mepirzepine; Mirtazepine; Mirtazapina [INN-Spanish]; Mirtazapine [Usan:Ban:Inn]
Brand:	Axit, Mirtabene, Remergon, Mirtazon, Promyrtil, Norset, Rexer, Remergil, Mirtaz, Remeron Soltab, Zispin, Remeron, Avanza
Category:	Histamine H1 Antagonists, Adrenergic alpha-Antagonists, Antidepressive Agents, Tricyclic
CAS number:	61337-67-5

Pharmacology

Indication:	For the treatment of major depressive disorder.
Pharmacology:	Mirtazapine, an antidepressant of the piperazinoazepine class, is a tetracyclic compound with an anxiolytic effect. Mirtazapine has fewer ADRs than tricyclic antidepressants and is better tolerated. Selective blockade of specific serotonin receptors by mirtazapine likey minimizes side effects typical of other antidepressants.
Mechanism of Action:	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-HT₁ rece... show more » 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-HT₁ receptors and contributing to the anxiolytic effects of mirtazapine. Mirtazapine also acts as a weak antagonist at 5-HT₁ receptors and as a potent antagonist at 5-HT₂ (particularly subtypes 2A and 2C) and 5-HT₃ 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. show less «
Absorption:	Rapid and complete, but, due to first-pass metabolism, absolute bioavailability is 50%.
Protein binding:	85%
Biotransformation:	Mirtazapine is extensively metabolized by demethylation and hydroxylation followed by glucuronide conjugation. Cytochrome P450 2D6 and cytochrome P450 1A2 are involved in formation of the 8-hydroxy metabolite of mirtazapine, and cytochrome P450 3A4 is responsible for the formation of the N-desmethyl and N-oxide metabolites. Several metabolites possess pharmacological activity, but plasma levels are very low.
Route of elimination:	This drug is known to be substantially excreted by the kidney (75%).
Half Life:	20-40 hours
Toxicity:	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]
Affected organisms:	Humans and other mammals

Interactions

Food interaction:

Take without regard to meals. Avoid alcohol.

Drug interaction:

Clonidine	Possible hypertensive crisis
Phenelzine	Possible severe adverse reaction with this combination
Tramadol	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Fluvoxamine	Fluvoxamine may increase the therapeutic and adverse effects of mirtazapine.
Zolmitriptan	Use of two serotonin modulators, such as zolmitriptan and mirtazapine, increases the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.

Clonidine	Possible hypertensive crisis
Phenelzine	Possible severe adverse reaction with this combination
Tramadol	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Fluvoxamine	Fluvoxamine may increase the therapeutic and adverse effects of mirtazapine.
Zolmitriptan	Use of two serotonin modulators, such as zolmitriptan and mirtazapine, increases the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.
Trimipramine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Triprolidine	The CNS depressants, Triprolidine and Mirtazapine, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
Terbinafine	Terbinafine may reduce the metabolism and clearance of Mirtazapine. Consider alternate therapy or monitor for therapeutic/adverse effects of Mirtazapine if Terbinafine is initiated, discontinued or dose changed.
Mephenytoin	The hydantoins may reduce mirtazapine plasma concentrations and pharmacological effects
Fosphenytoin	The hydantoins may reduce mirtazapine plasma concentrations and pharmacological effects
Galantamine	Possible antagonism of action
Phenytoin	The hydantoins may reduce mirtazapine plasma concentrations and pharmacological effects
Tranylcypromine	The MAO inhibitor, Tranylcypromine, may increase the central neurotoxic effects of the Mirtazapine. These agents should not be administered within 14 days of each other.
Venlafaxine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Isocarboxazid	Possible severe adverse reaction with this combination
Donepezil	Possible antagonism of action
Voriconazole	Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of mirtazapine by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of mirtazapine if voriconazole is initiated, discontinued or dose changed.
Rivastigmine	Possible antagonism of action
Rasagiline	Possible severe adverse reaction with this combination
Trazodone	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Telithromycin	Telithromycin may reduce clearance of Mirtazapine. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Mirtazapine if Telithromycin is initiated, discontinued or dose changed.
Ethotoin	The hydantoins may reduce mirtazapine plasma concentrations and pharmacological effects
Desvenlafaxine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

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Targets

5-hydroxytryptamine 2A receptor

5-hydroxytryptamine 3 receptor

Alpha-2A adrenergic receptor

5-hydroxytryptamine 2C receptor

Kappa-type opioid receptor

Histamine H1 receptor

Enzymes