PharmGKB: The Pharmacogenomics Knowledge Base

Drug/Small Molecule:
mirtazapine

2D structure

Overview

Generic Names: Mepirzepine; Mirtazapina [INN-Spanish]; Mirtazapine [Usan:Ban:Inn]; Mirtazapinum [INN-Latin]; Mirtazepine; mirtazapine
Trade Names: Avanza; Axit; Mirtabene; Mirtaz; Mirtazon; Norset; Promyrtil; Remergil; Remergon; Remeron; Remeron Soltab; Rexer; Zispin
PharmGKB Accession Id: PA450522

Description

Mirtazapine is an antidepressant introduced by Organon International in 1996 used for the treatment of moderate to severe depression. Mirtazapine has a tetracyclic chemical structure and is classified as a noradrenergic and specific serotonergic antidepressant (NaSSA). It is the only tetracyclic antidepressant that has been approved by the Food and Drug Administration to treat depression. Wikipedia (source: Drug Bank)

Indication

For the treatment of major depressive disorder. (source: Drug Bank)

ATC Therapeutic Category

  • N06AX:Other antidepressants

Pharmacology, Interactions, and Contraindications

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-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. (source: Drug Bank)

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. (source: Drug Bank)

Food Interactions

Take without regard to meals. Avoid alcohol. (source: Drug Bank)

Absorption, Distribution, Metabolism, Elimination & Toxicity

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. (source: Drug Bank)

Protein Binding

85% (source: Drug Bank)

Absorption

Rapid and complete, but, due to first-pass metabolism, absolute bioavailability is 50%. (source: Drug Bank)

Toxicity

Symptoms of overdose include disorientation, drowsiness, impaired memory, and tachycardia. LD<sub>50</sub>=mg/kg (orally in rat). (source: Drug Bank)

Isomeric SMILES Code:

CN1CCN2c3c(cccn3)Cc4ccccc4C2C1 (source: Drug Bank)

Curated Annotations (Curated Annotation)

  1. rs3800373 at chr6:35650454 in FKBP5
    This variant is associated with higher chance of response to anti-depressant drugs.
    Related Drugs:
    desipramine, fluoxetine, mirtazapine, venlafaxine
    Related Diseases:
    Depression
    Evidence:
    PMID:15565110
    PMID:18349090
    PMID:18597649
  2. rs1360780 at chr6:35715549 in FKBP5
    This variant is associated with higher chance of response to anti-depressant drugs.
    Related Drugs:
    desipramine, fluoxetine, mirtazapine, venlafaxine
    Related Diseases:
    Depression
    Evidence:
    PMID:15565111
    PMID:18349090
    PMID:18597649
  3. rs10897346 at chr11:55387401
    This SNP was significantly associated with response to therapy in 182 patient who received treatment for major depression.
    Related Drugs:
    mirtazapine, venlafaxine
    Related Diseases:
    Depression
    Evidence:
    PMID:18496129
  4. rs1487278 at chr12:70687118 in TPH2
    This SNP was significantly associated with response to therapy in 182 patient who received treatment for major depression.
    Related Drugs:
    mirtazapine, venlafaxine
    Related Diseases:
    Depression
    Evidence:
    PMID:18496129
Variant names are different names that have been used in the literature and other resources to refer to the same variant.

The following genes are in curated knowledge about this drug.

  Gene Relationship Evidence
No phenotype data Genotype Data Available Literature annotations available Not annotated
CYP1A2
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2D6
  •   
  • PD
  • PK
  •   
  • GN
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
CYP3A
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP3A4
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP3A5
  •   
  •   
  • PK
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
FKBP5
  • CO
  •   
  •   
  •   
  • GN
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
HRH1
  •   
  • PD
  • PK
  • FA
  •   
Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
MAOB
  •   
  •   
  •   
  •   
  • GN
Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
SLC6A3
  •   
  • PD
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
SLC6A4
  • CO
  • PD
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
TPH2
  •   
  •   
  •   
  •   
  •   
Variants

A list of non-curated publications that mention this drug along with other genes is available.

Drug Targets

Gene Description
HTR1A Uncurated Annotation (source: Drug Bank)
HTR2A Uncurated Annotation (source: Drug Bank)
HTR2C Uncurated Annotation (source: Drug Bank)
HTR3A Uncurated Annotation (source: Drug Bank)
ADRA2A Uncurated Annotation (source: Drug Bank)
HRH1 Uncurated Annotation (source: Drug Bank)
OPRK1 Uncurated Annotation (source: Drug Bank)

The following drugs are in curated knowledge about this drug.

  Drug Relationship Evidence
Phenotype data available Genotype Data Available Literature annotations available Not annotated
tamoxifen
  •   
  •   
  •   
  •   
  •   
Publications

A list of non-curated publications that mention this drug along with other drugs is available.

Drug Interactions

Drug Description
clonidine Uncurated Annotation Possible hypertensive crisis (source: Drug Bank)
donepezil Uncurated Annotation Possible antagonism of action (source: Drug Bank)
fluvoxamine Uncurated Annotation Fluvoxamine increases the effect and toxicity of mirtazapine (source: Drug Bank)
galantamine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
isocarboxazid Uncurated Annotation Possible severe adverse reaction with this combination (source: Drug Bank)
mephenytoin Uncurated Annotation The hydantoins may reduce mirtazapine plasma concentrations and pharmacological effects (source: Drug Bank)
phenelzine Uncurated Annotation Possible severe adverse reaction with this combination (source: Drug Bank)
phenytoin Uncurated Annotation The hydantoins may reduce mirtazapine plasma concentrations and pharmacological effects (source: Drug Bank)
rivastigmine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
tranylcypromine Uncurated Annotation Possible severe adverse reaction with this combination (source: Drug Bank)

Curated Information

The following diseases are in curated knowledge about this drug.

  Disease Relationship Evidence
Phenotype data available No genotype data Literature annotations available Not annotated
Depression
  • CO
  • PD
  •   
  •   
  • GN
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
Depression, Postpartum
  • CO
  •   
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Depressive Disorder
  • CO
  •   
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Depressive Disorder, Major
  • CO
  •   
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Hallucinations
  • CO
  •   
  •   
  •   
  •   
Publications

Non-Curated Information

A list of non-curated publications that mention this drug along with other diseases is available.

Additional Datasets

These datasets are minimally curated and are sorted alphabetically by title.

  1. Genetic Variants in Tricyclic Antidepressant associated Adverse Events
  2. Physicochemical determinants of human renal clearance

LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB00370
KEGG Compound ID:
C07570
KEGG Drug ID:
D00563
PubChem Compound ID:
4205
PubChem Substance ID:
183976

Common Searches

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Non-Curated Publications

A list of non-curated publications that mention this drug is available.

PharmGKB integrates drug information from different sources: DrugBank, Open Eye Scientific Software.
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