5-methyl-2,5,19-triazatetracyclo[13.4.0.02,7.08,13]nonadeca-1(15),8,10,12,16,18-hexaene

• ChemBase ID: 254
• Molecular Formular: C17H19N3
• Molecular Mass: 265.35286
• Monoisotopic Mass: 265.15789762
• SMILES: N12C(CN(CC1)C)c1c(Cc3c2nccc3)cccc1
• Canonical SMILES: CN1CCN2C(C1)c1ccccc1Cc1c2nccc1
• InChI: 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
• InChIKey: RONZAEMNMFQXRA-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 5-methyl-2,5,19-triazatetracyclo[13.4.0.0^2,^7.0^8,^1^3]nonadeca-1(15),8,10,12,16,18-hexaene; 5-methyl-2,5,19-triazatetracyclo[13.4.0.0^{2,7}.0^{8,13}]nonadeca-1(15),8(13),9,11,16,18-hexaene; 5-methyl-2,5,19-triazatetracyclo[13.4.0.0^2,^7.0^8,^1^3]nonadeca-1(15),8(13),9,11,16,18-hexaene; 5-methyl-2,5,19-triazatetracyclo[13.4.0.0^{2,7}.0^{8,13}]nonadeca-1(19),8(13),9,11,15,17-hexaene
• IUPAC Traditional name: mirtazapine; 5-methyl-2,5,19-triazatetracyclo[13.4.0.0^{2,7}.0^{8,13}]nonadeca-1(15),8(13),9,11,16,18-hexaene; 5-methyl-2,5,19-triazatetracyclo[13.4.0.0^{2,7}.0^{8,13}]nonadeca-1(19),8(13),9,11,15,17-hexaene
• Brand Name: Remeron; Remeron Soltab; Zispin; Remergil; Norset; Rexer; Remergon; Mirtabene; Avanza; Mirtazon; Axit; Mirtaz; Promyrtil; Remeron, Avanza, Zispin
• Synonyms: Esmirtazapine; 1,2,3,4,10,14b-Hexahydro-2-methylpyrazino[2,1-a]pyrido[2,3-c][2]benzazepine; Mirtazapine; Remeron; Avanza; 5-methyl-2,5,19-triazatetracyclo[13.4.0.0^{2,7}.0^{8,13}]nonadeca-1(15),8(13),9,11,16,18-hexaene; Org-3770; Zispin; Mirtazapina [INN-Spanish]; Mirtazapine [Usan:Ban:Inn]; Mirtazapinum [INN-Latin]; Mirtazepine; Mepirzepine; mirtazapine; Mirtazapine; 6-Azamianserin; Org 3770

Database IDs

• CAS Number: 61337-67-5; 61337-87-9; 85650-52-8
• MDL Number: MFCD00865427
• PubChem SID: 160963717; 24724531; 46506965
• PubChem CID: 4205; 6451144
• CHEBI ID: 6950
• ATC CODE: N06AX11
• CHEMBL: 654
• Chemspider ID: 2342166; 4060
• DrugBank ID: DB00370
• KEGG ID: D00563; D04055
• Unique Ingredient Identifier: 4685R51V7M; A051Q2099Q
• Wikipedia Title: Mirtazapine; Esmirtazapine
• Medline Plus: a697009

CALCULATED PROPERTIES

JChem

• H Acceptors: 3
• H Donor: 0
• LogD (pH = 5.5): 1.8185004
• LogD (pH = 7.4): 3.133914
• Log P: 3.2079828
• Molar Refractivity: 82.6553 cm^3
• Polarizability: 31.225294 Å^3
• Polar Surface Area: 19.37 Å^2
• Rotatable Bonds: 0
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 2.9
• LOG S: -2.38
• Solubility (Water): 1.10e+00 g/l

PROPERTIES

Physical Property

• Solubility: Chloroform; DMSO: soluble ~8 mg/mL; Slight; Soluble in methanol and chloroform
• Apperance: white powder; White Solid
• Melting Point: 114-116 °C (237.2-240.8°F); 114-116°C
• Boiling Point: 432°C (809.6°F)
• Density: 1.22 g/cm^3
• Hydrophobicity(logP): 2.814; 2.9

Safety Information

• Storage Condition: -20°C; -20°C Freezer
• German water hazard class: 3
• Personal Protective Equipment: Eyeshields, Gloves, type N95 (US), type P1 (EN143) respirator filter

Pharmacology Properties

• Admin Routes: Oral
• Bioavailability: 50%
• Excretion: Urine (75%); Feces (15%)
• Half Life: 20–40 hours
• Metabolism: Liver (CYP1A2, CYP2D6, and CYP3A4); Liver (CYP2D6)
• Protein Bound: 85%
• Legal Status: Rx-only; Uncontrolled
• Pregnancy Category: C
• Gene Information: human ... ADRA2A(150), ADRA2C(152), DRD2(1813), DRD3(1814), DRD4(1815), HRH1(3269), HTR1A(3350), HTR2A(3356), HTR2C(3358), HTR7(3363)mouse ... Slc6a2(20538)rat ... Adra1a(29412), Drd1a(24316), Drd2(24318), Htr1a(24473), Htr2a(29595), Htr2c(25187), Slc6a3(24898), Slc6a4(25553)

Product Information

• Purity: ≥98% (HPLC); 95%
• Salt Data: Free Base
• Empirical Formula (Hill Notation): C17H19N3

DETAILS

DrugBank - DB00370

• Drug Groups: approved
• 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]
• 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.
• 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
• 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.
• Absorption: Rapid and complete, but, due to first-pass metabolism, absolute bioavailability is 50%.
• Half Life: 20-40 hours
• Protein Binding: 85%
• Elimination: This drug is known to be substantially excreted by the kidney (75%).
• References: 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. [Pubmed] ; Burrows GD, Kremer CM: Mirtazapine: clinical advantages in the treatment of depression. J Clin Psychopharmacol. 1997 Apr;17 Suppl 1:34S-39S. [Pubmed] ; Velazquez C, Carlson A, Stokes KA, Leikin JB: Relative safety of mirtazapine overdose. Vet Hum Toxicol. 2001 Dec;43(6):342-4. [Pubmed] ; Gorman JM: Mirtazapine: clinical overview. J Clin Psychiatry. 1999;60 Suppl 17:9-13; discussion 46-8. [Pubmed] ; 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. [Pubmed] ; [Pubmed]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

Selleck Chemicals - S2016

Research Area: Neurological Disease
Biological Activity:
Mirtazapine (Remeron, Avanza) is a potent tetracyclic antidepressant. Mirtazapine (Remeron, Avanza) used primarily in the treatment of depression. It is also sometimes used as a hypnotic, antiemetic, and appetite stimulant, and for the treatment of anxiety, among other indications. In addition, along with its close analogues mianserin and setiptiline, mirtazapine (Remeron, Avanza) is one of the few noradrenergic and specific serotonergic antidepressants (NaSSAs). Additionally, the (S)-(+)-enantiomer of mirtazapine, which is also called esmirtazapine, is currently under development for the treatment of insomnia and menopausal symptoms. Mirtazapine’s primary use is the treatment of major depressive disorder. Mirtazapine (Remeron, Avanza) has been found to be useful in the treatment of many diseases, including generalized anxiety disorder, social anxiety disorder, obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder, seasonal affective disorder, insomnia, nausea and vomiting, diminished appetite and associated weight loss, and itching as well. [1]References on Mirtazapine (Remeron, Avanza)[1] http://en.wikipedia.org/wiki/Mirtazapine, ,

Sigma Aldrich - M0443

Biochem/physiol Actions
Mirtazapine is a noradrenergic and specific serotonergic antidepressant (NaSSA). Mirtazapine agonizes selective adrenergic and serotonergic receptors so that both NE release and 5-HT1A mediated serotonergic signaling are increased.

Toronto Research Chemicals - M365000

An α2-Adrenergic blocker; analogue of Mianserin. Antidepressant.

REFERENCES

• 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. Pubmed
• Burrows GD, Kremer CM: Mirtazapine: clinical advantages in the treatment of depression. J Clin Psychopharmacol. 1997 Apr;17 Suppl 1:34S-39S. Pubmed
• Velazquez C, Carlson A, Stokes KA, Leikin JB: Relative safety of mirtazapine overdose. Vet Hum Toxicol. 2001 Dec;43(6):342-4. Pubmed
• 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. Pubmed
• Gorman JM: Mirtazapine: clinical overview. J Clin Psychiatry. 1999;60 Suppl 17:9-13; discussion 46-8. Pubmed
• Pubmed
• http://en.wikipedia.org/wiki/Mirtazapine
• De Boer, T., et al.: Neuropharmacology, 27, 399 (1988)
• Smith, W.T., et al.: Psychopharmacol. Bull., 26, 191 (1990)