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Record Information
Version3.6
Creation Date2012-09-06 15:16:49 UTC
Update Date2016-02-11 01:28:48 UTC
HMDB IDHMDB14514
Secondary Accession NumbersNone
Metabolite Identification
Common NameMirtazapine
DescriptionMirtazapine 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]
Structure
Thumb
Synonyms
ValueSource
1,2,3,4,10,14b-hexahydro-2-methylpyrazino(2,1-a)pyrido(2,3-c)BenzazepineChEBI
MirtazapinaChEBI
MirtazapinumChEBI
MepirzepineHMDB
MirtazepineHMDB
Chemical FormulaC17H19N3
Average Molecular Weight265.3529
Monoisotopic Molecular Weight265.157897623
IUPAC Name5-methyl-2,5,19-triazatetracyclo[13.4.0.0²,⁷.0⁸,¹³]nonadeca-1(15),8,10,12,16,18-hexaene
Traditional Namemirtazapine
CAS Registry Number61337-67-5
SMILES
CN1CCN2C(C1)C1=CC=CC=C1CC1=C2N=CC=C1
InChI Identifier
InChI=1S/C17H19N3/c1-19-9-10-20-16(12-19)15-7-3-2-5-13(15)11-14-6-4-8-18-17(14)20/h2-8,16H,9-12H2,1H3
InChI KeyInChIKey=RONZAEMNMFQXRA-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as piperazinoazepines. These are compounds containing a piperazinoazepine skeleton, which consists of an azepie ring fused to a piperazine.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPiperazinoazepines
Sub ClassNot Available
Direct ParentPiperazinoazepines
Alternative Parents
Substituents
  • Piperazino-azepine
  • Benzazepine
  • Dialkylarylamine
  • Aralkylamine
  • N-alkylpiperazine
  • N-methylpiperazine
  • Azepine
  • Imidolactam
  • Benzenoid
  • Pyridine
  • Piperazine
  • 1,4-diazinane
  • Heteroaromatic compound
  • Tertiary aliphatic amine
  • Tertiary amine
  • Azacycle
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Ontology
StatusExpected but not Quantified
Origin
  • Drug
Biofunction
  • Adrenergic alpha-Antagonists
  • Antidepressive Agents, Tricyclic
  • Histamine H1 Antagonists
Application
  • Pharmaceutical
Cellular locations
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point114 - 116 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility1.10e+00 g/LNot Available
LogP2.9Not Available
Predicted Properties
PropertyValueSource
Water Solubility1.1 mg/mLALOGPS
logP2.9ALOGPS
logP3.21ChemAxon
logS-2.4ALOGPS
pKa (Strongest Basic)6.67ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area19.37 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity82.66 m3·mol-1ChemAxon
Polarizability30.35 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Biological Properties
Cellular Locations
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00370
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00370
  • Not Applicable
details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiofluidValueOriginal ageOriginal sexOriginal conditionComments
Blood0-4 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0-2 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00370
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID4060
KEGG Compound IDC07570
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkMirtazapine
NuGOwiki LinkHMDB14514
Metagene LinkHMDB14514
METLIN IDNot Available
PubChem Compound4205
PDB IDNot Available
ChEBI ID6950
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Gorman JM: Mirtazapine: clinical overview. J Clin Psychiatry. 1999;60 Suppl 17:9-13; discussion 46-8. [10446735 ]
  2. Burrows GD, Kremer CM: Mirtazapine: clinical advantages in the treatment of depression. J Clin Psychopharmacol. 1997 Apr;17 Suppl 1:34S-39S. [9090576 ]
  3. Fawcett J, Barkin RL: Review of the results from clinical studies on the efficacy, safety and tolerability of mirtazapine for the treatment of patients with major depression. J Affect Disord. 1998 Dec;51(3):267-85. [10333982 ]
  4. Velazquez C, Carlson A, Stokes KA, Leikin JB: Relative safety of mirtazapine overdose. Vet Hum Toxicol. 2001 Dec;43(6):342-4. [11757992 ]
  5. Baldwin DS, Anderson IM, Nutt DJ, Bandelow B, Bond A, Davidson JR, den Boer JA, Fineberg NA, Knapp M, Scott J, Wittchen HU: Evidence-based guidelines for the pharmacological treatment of anxiety disorders: recommendations from the British Association for Psychopharmacology. J Psychopharmacol. 2005 Nov;19(6):567-96. [16272179 ]
  6. Gillman PK: A systematic review of the serotonergic effects of mirtazapine in humans: implications for its dual action status. Hum Psychopharmacol. 2006 Mar;21(2):117-25. [16342227 ]

Enzymes

General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
References
  1. Anttila SA, Leinonen EV: A review of the pharmacological and clinical profile of mirtazapine. CNS Drug Rev. 2001 Fall;7(3):249-64. [11607047 ]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. [19934256 ]
  3. Stormer E, von Moltke LL, Shader RI, Greenblatt DJ: Metabolism of the antidepressant mirtazapine in vitro: contribution of cytochromes P-450 1A2, 2D6, and 3A4. Drug Metab Dispos. 2000 Oct;28(10):1168-75. [10997935 ]
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular weight:
55627.365
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. [19934256 ]
General function:
Involved in monooxygenase activity
Specific function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular weight:
55768.94
References
  1. Anttila SA, Leinonen EV: A review of the pharmacological and clinical profile of mirtazapine. CNS Drug Rev. 2001 Fall;7(3):249-64. [11607047 ]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. [19934256 ]
  3. Stormer E, von Moltke LL, Shader RI, Greenblatt DJ: Metabolism of the antidepressant mirtazapine in vitro: contribution of cytochromes P-450 1A2, 2D6, and 3A4. Drug Metab Dispos. 2000 Oct;28(10):1168-75. [10997935 ]
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular weight:
58406.915
References
  1. Anttila SA, Leinonen EV: A review of the pharmacological and clinical profile of mirtazapine. CNS Drug Rev. 2001 Fall;7(3):249-64. [11607047 ]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. [19934256 ]
  3. Stormer E, von Moltke LL, Shader RI, Greenblatt DJ: Metabolism of the antidepressant mirtazapine in vitro: contribution of cytochromes P-450 1A2, 2D6, and 3A4. Drug Metab Dispos. 2000 Oct;28(10):1168-75. [10997935 ]
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti-cancer drug paclitaxel (taxol).
Gene Name:
CYP2C8
Uniprot ID:
P10632
Molecular weight:
55824.275
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. [19934256 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
Alpha-2 adrenergic receptors mediate the catecholamine- induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol
Gene Name:
ADRA2A
Uniprot ID:
P08913
Molecular weight:
48956.3
References
  1. Garcia-Sevilla JA, Ventayol P, Perez V, Rubovszky G, Puigdemont D, Ferrer-Alcon M, Andreoli A, Guimon J, Alvarez E: Regulation of platelet alpha 2A-adrenoceptors, Gi proteins and receptor kinases in major depression: effects of mirtazapine treatment. Neuropsychopharmacology. 2004 Mar;29(3):580-8. [14628003 ]
  2. Anttila SA, Leinonen EV: A review of the pharmacological and clinical profile of mirtazapine. CNS Drug Rev. 2001 Fall;7(3):249-64. [11607047 ]
  3. Besson A, Haddjeri N, Blier P, de Montigny C: Effects of the co-administration of mirtazapine and paroxetine on serotonergic neurotransmission in the rat brain. Eur Neuropsychopharmacol. 2000 May;10(3):177-88. [10793320 ]
  4. Schreiber S, Bleich A, Pick CG: Venlafaxine and mirtazapine: different mechanisms of antidepressant action, common opioid-mediated antinociceptive effects--a possible opioid involvement in severe depression? J Mol Neurosci. 2002 Feb-Apr;18(1-2):143-9. [11931344 ]
  5. Rogoz Z, Wrobel A, Dlaboga D, Maj J, Dziedzicka-Wasylewska M: Effect of repeated treatment with mirtazapine on the central alpha1-adrenergic receptors. J Physiol Pharmacol. 2002 Mar;53(1):105-16. [11939713 ]
  6. Rogoz Z, Wrobel A, Dlaboga D, Dziedzicka-Wasylewska M: Effect of repeated treatment with mirtazapine on the central dopaminergic D2/D3 receptors. Pol J Pharmacol. 2002 Jul-Aug;54(4):381-9. [12523492 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. This receptor is involved in tracheal smooth muscle contraction, bronchoconstriction, and control of aldosterone production
Gene Name:
HTR2A
Uniprot ID:
P28223
Molecular weight:
52602.6
References
  1. Westenberg HG: Pharmacology of antidepressants: selectivity or multiplicity? J Clin Psychiatry. 1999;60 Suppl 17:4-8; discussion 46-8. [10446734 ]
  2. Gorman JM: Mirtazapine: clinical overview. J Clin Psychiatry. 1999;60 Suppl 17:9-13; discussion 46-8. [10446735 ]
  3. Nutt DJ: Care of depressed patients with anxiety symptoms. J Clin Psychiatry. 1999;60 Suppl 17:23-7; discussion 46-8. [10446738 ]
  4. Laakmann G, Schule C, Baghai T, Waldvogel E: Effects of mirtazapine on growth hormone, prolactin, and cortisol secretion in healthy male subjects. Psychoneuroendocrinology. 1999 Oct;24(7):769-84. [10451911 ]
  5. Waldinger MD, Berendsen HH, Schweitzer DH: Treatment of hot flushes with mirtazapine: four case reports. Maturitas. 2000 Oct 31;36(3):165-8. [11063897 ]
  6. Anttila SA, Leinonen EV: A review of the pharmacological and clinical profile of mirtazapine. CNS Drug Rev. 2001 Fall;7(3):249-64. [11607047 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system
Gene Name:
HTR2C
Uniprot ID:
P28335
Molecular weight:
51820.7
References
  1. Benelli A, Frigeri C, Bertolini A, Genedani S: Influence of mirtazapine on the sexual behavior of male rats. Psychopharmacology (Berl). 2004 Jan;171(3):250-8. Epub 2003 Nov 13. [14615872 ]
  2. Millan MJ, Gobert A, Rivet JM, Adhumeau-Auclair A, Cussac D, Newman-Tancredi A, Dekeyne A, Nicolas JP, Lejeune F: Mirtazapine enhances frontocortical dopaminergic and corticolimbic adrenergic, but not serotonergic, transmission by blockade of alpha2-adrenergic and serotonin2C receptors: a comparison with citalopram. Eur J Neurosci. 2000 Mar;12(3):1079-95. [10762339 ]
  3. Meert TF, Melis W, Aerts N, Clincke G: Antagonism of meta-chlorophenylpiperazine-induced inhibition of exploratory activity in an emergence procedure, the open field test, in rats. Behav Pharmacol. 1997 Aug;8(4):353-63. [9832994 ]
  4. Millan MJ: Serotonin 5-HT2C receptors as a target for the treatment of depressive and anxious states: focus on novel therapeutic strategies. Therapie. 2005 Sep-Oct;60(5):441-60. [16433010 ]
  5. Dekeyne A, Iob L, Millan MJ: Following long-term training with citalopram, both mirtazapine and mianserin block its discriminative stimulus properties in rats. Psychopharmacology (Berl). 2001 Jan;153(3):389-92. [11271412 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system
Gene Name:
HRH1
Uniprot ID:
P35367
Molecular weight:
55783.6
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
General function:
Involved in extracellular ligand-gated ion channel activity
Specific function:
This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor is a ligand-gated ion channel, which when activated causes fast, depolarizing responses in neurons. It is a cation-specific, but otherwise relatively nonselective, ion channel
Gene Name:
HTR3A
Uniprot ID:
P46098
Molecular weight:
55279.8
References
  1. Westenberg HG: Pharmacology of antidepressants: selectivity or multiplicity? J Clin Psychiatry. 1999;60 Suppl 17:4-8; discussion 46-8. [10446734 ]
  2. Gorman JM: Mirtazapine: clinical overview. J Clin Psychiatry. 1999;60 Suppl 17:9-13; discussion 46-8. [10446735 ]
  3. Kast RE, Foley KF: Cancer chemotherapy and cachexia: mirtazapine and olanzapine are 5-HT3 antagonists with good antinausea effects. Eur J Cancer Care (Engl). 2007 Jul;16(4):351-4. [17587360 ]
  4. de Boer T: The effects of mirtazapine on central noradrenergic and serotonergic neurotransmission. Int Clin Psychopharmacol. 1995 Dec;10 Suppl 4:19-23. [8930006 ]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  6. Anttila SA, Leinonen EV: A review of the pharmacological and clinical profile of mirtazapine. CNS Drug Rev. 2001 Fall;7(3):249-64. [11607047 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Receptor for dynorphins. May play a role in arousal and regulation of autonomic and neuroendocrine functions
Gene Name:
OPRK1
Uniprot ID:
P41145
Molecular weight:
42644.7
References
  1. Schreiber S, Rigai T, Katz Y, Pick CG: The antinociceptive effect of mirtazapine in mice is mediated through serotonergic, noradrenergic and opioid mechanisms. Brain Res Bull. 2002 Sep 30;58(6):601-5. [12372565 ]