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

• ChemBase编号: 254
• 分子式: C17H19N3
• 平均质量: 265.35286
• 单一同位素质量: 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

名称和登记号

名称

• IUPAC标准名: 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传统名: 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
• 商标名: Remeron; Remeron Soltab; Zispin; Remergil; Norset; Rexer; Remergon; Mirtabene; Avanza; Mirtazon; Axit; Mirtaz; Promyrtil; Remeron, Avanza, Zispin
• 别名: 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

登记号

• CAS号: 61337-87-9; 85650-52-8; 61337-67-5
• MDL号: MFCD00865427
• PubChem SID: 46506965; 160963717; 24724531
• PubChem CID: 6451144; 4205
• CHEBI ID: 6950
• ATC码: N06AX11
• CHEMBL: 654
• Chemspider ID: 4060; 2342166
• DrugBank ID: DB00370
• KEGG ID: D00563; D04055
• 美国药典/FDA物质标识码: 4685R51V7M; A051Q2099Q
• 维基百科标题: Mirtazapine; Esmirtazapine
• Medline Plus: a697009

理论计算性质

JChem

• 质子受体: 3
• 质子供体: 0
• LogD (pH = 5.5): 1.8185004
• LogD (pH = 7.4): 3.133914
• Log P: 3.2079828
• 摩尔折射率: 82.6553 cm^3
• 极化性: 31.225294 Å^3
• 极化表面积: 19.37 Å^2
• 可自由旋转的化学键: 0
• 里宾斯基五规则: true

ALOGPS 2.1

• Log P: 2.9
• LOG S: -2.38
• 溶解度: 1.10e+00 g/l

分子性质

理化性质

• 溶解度: Chloroform; DMSO: soluble ~8 mg/mL; Slight; Soluble in methanol and chloroform
• 外观: white powder; White Solid
• 熔点: 114-116 °C (237.2-240.8°F); 114-116°C
• 沸点: 432°C (809.6°F)
• 密度: 1.22 g/cm^3
• 疏水性(logP): 2.814; 2.9

安全信息

• 保存条件: -20°C; -20°C Freezer
• 德国WGK号: 3
• 个人保护装置: Eyeshields, Gloves, type N95 (US), type P1 (EN143) respirator filter

药理学性质

• 给药途径: Oral
• 生物利用度: 50%
• 排泄: Urine (75%); Feces (15%)
• 半衰期: 20–40 hours
• 代谢: Liver (CYP1A2, CYP2D6, and CYP3A4); Liver (CYP2D6)
• 蛋白结合率: 85%
• 法定药品分级: Rx-only; Uncontrolled
• 妊娠期药物分类: C
• 相关基因信息: 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)

产品相关信息

• 纯度: ≥98% (HPLC); 95%
• 成盐信息: Free Base
• Empirical Formula (Hill Notation): C17H19N3

详细说明

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.

参考文献

• 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)