(1R,2S)-2-(aminomethyl)-N,N-diethyl-1-phenylcyclopropane-1-carboxamide

• ChemBase编号: 4398
• 分子式: C15H22N2O
• 平均质量: 246.34798
• 单一同位素质量: 246.17321333
• SMILES: O=C(N(CC)CC)[C@]1([C@H](C1)CN)c1ccccc1
• Canonical SMILES: NC[C@H]1C[C@@]1(c1ccccc1)C(=O)N(CC)CC
• InChI: InChI=1S/C15H22N2O/c1-3-17(4-2)14(18)15(10-13(15)11-16)12-8-6-5-7-9-12/h5-9,13H,3-4,10-11,16H2,1-2H3/t13-,15+/m1/s1
• InChIKey: GJJFMKBJSRMPLA-HIFRSBDPSA-N

名称和登记号

名称

• IUPAC标准名: (1R,2S)-2-(aminomethyl)-N,N-diethyl-1-phenylcyclopropane-1-carboxamide
• IUPAC传统名: milnacipran
• 商标名: Ixel; Toledomin
• 别名: Milnacipranum [latin]; Midalcipran; (-)-milnacipran; F 2207; milnacipran; Milnacipran

登记号

• CAS号: 92623-85-3
• PubChem SID: 160967830; 46506141
• PubChem CID: 65833
• ATC码: N06AX17
• CHEMBL: 252923
• Chemspider ID: 59245
• DrugBank ID: DB04896
• KEGG ID: D08222
• 美国药典/FDA物质标识码: G56VK1HF36
• 维基百科标题: Milnacipran
• Medline Plus: a609016

理论计算性质

JChem

• 质子受体: 2
• 质子供体: 1
• LogD (pH = 5.5): -1.5899252
• LogD (pH = 7.4): -0.91125065
• Log P: 1.4217067
• 摩尔折射率: 73.8095 cm^3
• 极化性: 28.916954 Å^3
• 极化表面积: 46.33 Å^2
• 可自由旋转的化学键: 5
• 里宾斯基五规则: true

ALOGPS 2.1

• Log P: 1.72
• LOG S: -2.3
• 溶解度: 1.23e+00 g/l

分子性质

药理学性质

• 给药途径: Oral
• 生物利用度: 85%
• 排泄: Renal
• 半衰期: 8 hours
• 代谢: Hepatic
• 蛋白结合率: 13%
• 法定药品分级: Rx-only (US)
• 妊娠期药物分类: X (US)

详细说明

DrugBank - DB04896

• Drug Groups: approved; investigational
• Description: Milnacipran is an antidepressant of the serotonin-norepinephrine reuptake inhibitor class. Milnacipran has been approved and sold in Austria since September 1998 under the brand name Ixel. Cypress Bioscience bought the exclusive rights for approval and marketing of the drug for any purpose in the US and Canada in 2003 from the manufacturer Pierre Fabre; the approval procedure in both countries is ongoing.
• Indication: Milnacipran is used to treat moderate to severe clinical depression and chronic pain.
• Affected Organisms: Humans and other mammals
• Biotransformation: Only traces of active metabolites are found. Cytochrome P450 enzymes play no role in the metabolism of Milnacipran.
• Absorption: Milnacipran is well absorbed following oral administration with an absolute bioavailability of 85%. Meals have no effect on absorption.
• Half Life: 8 hours
• Elimination: It is excreted predominantly unchanged in urine (55%) and has a terminal elimination half-life of about 6 to 8 hours. The main route of elimination of bepotastine besilate is urinary excretion (with approximately 75-90% excreted unchanged in urine).
• Distribution: * 400 L
• References: Leo RJ, Brooks VL: Clinical potential of milnacipran, a serotonin and norepinephrine reuptake inhibitor, in pain. Curr Opin Investig Drugs. 2006 Jul;7(7):637-42. [Pubmed] ; Sato S, Yamakawa Y, Terashima Y, Ohta H, Asada T: Efficacy of milnacipran on cognitive dysfunction with post-stroke depression: preliminary open-label study. Psychiatry Clin Neurosci. 2006 Oct;60(5):584-9. [Pubmed] ; Simon LS: Is milnacipran effective in treating pain in patients with fibromyalgia? Nat Clin Pract Rheumatol. 2006 Mar;2(3):126-7. [Pubmed] ; Soya A, Terao T, Nakajima M, Kojima H, Okamoto T, Inoue Y, Iwakawa M, Shinkai K, Yoshimura R, Ueta Y, Nakamura J: Effects of repeated milnacipran administration on brain serotonergic and noradrenergic functions in healthy volunteers. Psychopharmacology (Berl). 2006 Sep;187(4):526-7. Epub 2006 Jul 8. [Pubmed] ; King T, Rao S, Vanderah T, Chen Q, Vardanyan A, Porreca F: Differential blockade of nerve injury-induced shift in weight bearing and thermal and tactile hypersensitivity by milnacipran. J Pain. 2006 Jul;7(7):513-20. [Pubmed] ; Moojen VK, Martins MR, Reinke A, Feier G, Agostinho FR, Cechin EM, Quevedo J: Effects of milnacipran in animal models of anxiety and memory. Neurochem Res. 2006 Apr;31(4):571-7. Epub 2006 May 9. [Pubmed] ; Moret C, Charveron M, Finberg JP, Couzinier JP, Briley M: Biochemical profile of midalcipran (F 2207), 1-phenyl-1-diethyl-aminocarbonyl-2-aminomethyl-cyclopropane (Z) hydrochloride, a potential fourth generation antidepressant drug. Neuropharmacology. 1985 Dec;24(12):1211-9. [Pubmed] ; Briley M, Prost JF, Moret C: Preclinical pharmacology of milnacipran. Int Clin Psychopharmacol. 1996 Sep;11 Suppl 4:9-14. [Pubmed] ; Puozzo C, Panconi E, Deprez D: Pharmacology and pharmacokinetics of milnacipran. Int Clin Psychopharmacol. 2002 Jun;17 Suppl 1:S25-35. [Pubmed] ; Leinonen E, Lepola U, Koponen H, Mehtonen OP, Rimon R: Long-term efficacy and safety of milnacipran compared to clomipramine in patients with major depression. Acta Psychiatr Scand. 1997 Dec;96(6):497-504. [Pubmed] ; Papakostas GI, Fava M: A meta-analysis of clinical trials comparing milnacipran, a serotonin--norepinephrine reuptake inhibitor, with a selective serotonin reuptake inhibitor for the treatment of major depressive disorder. Eur Neuropsychopharmacol. 2007 Jan;17(1):32-6. Epub 2006 Jun 8. [Pubmed] ; Kako Y, Niwa Y, Toyomaki A, Yamanaka H, Kitagawa N, Denda K, Koyama T: A case of adult attention-deficit/hyperactivity disorder alleviated by milnacipran. Prog Neuropsychopharmacol Biol Psychiatry. 2007 Apr 13;31(3):772-5. Epub 2007 Jan 12. [Pubmed]
• External Links: Wikipedia; Drugs.com

参考文献

• Leo RJ, Brooks VL: Clinical potential of milnacipran, a serotonin and norepinephrine reuptake inhibitor, in pain. Curr Opin Investig Drugs. 2006 Jul;7(7):637-42. Pubmed
• Sato S, Yamakawa Y, Terashima Y, Ohta H, Asada T: Efficacy of milnacipran on cognitive dysfunction with post-stroke depression: preliminary open-label study. Psychiatry Clin Neurosci. 2006 Oct;60(5):584-9. Pubmed
• Simon LS: Is milnacipran effective in treating pain in patients with fibromyalgia? Nat Clin Pract Rheumatol. 2006 Mar;2(3):126-7. Pubmed
• Soya A, Terao T, Nakajima M, Kojima H, Okamoto T, Inoue Y, Iwakawa M, Shinkai K, Yoshimura R, Ueta Y, Nakamura J: Effects of repeated milnacipran administration on brain serotonergic and noradrenergic functions in healthy volunteers. Psychopharmacology (Berl). 2006 Sep;187(4):526-7. Epub 2006 Jul 8. Pubmed
• King T, Rao S, Vanderah T, Chen Q, Vardanyan A, Porreca F: Differential blockade of nerve injury-induced shift in weight bearing and thermal and tactile hypersensitivity by milnacipran. J Pain. 2006 Jul;7(7):513-20. Pubmed
• Moojen VK, Martins MR, Reinke A, Feier G, Agostinho FR, Cechin EM, Quevedo J: Effects of milnacipran in animal models of anxiety and memory. Neurochem Res. 2006 Apr;31(4):571-7. Epub 2006 May 9. Pubmed
• Moret C, Charveron M, Finberg JP, Couzinier JP, Briley M: Biochemical profile of midalcipran (F 2207), 1-phenyl-1-diethyl-aminocarbonyl-2-aminomethyl-cyclopropane (Z) hydrochloride, a potential fourth generation antidepressant drug. Neuropharmacology. 1985 Dec;24(12):1211-9. Pubmed
• Briley M, Prost JF, Moret C: Preclinical pharmacology of milnacipran. Int Clin Psychopharmacol. 1996 Sep;11 Suppl 4:9-14. Pubmed
• Puozzo C, Panconi E, Deprez D: Pharmacology and pharmacokinetics of milnacipran. Int Clin Psychopharmacol. 2002 Jun;17 Suppl 1:S25-35. Pubmed
• Leinonen E, Lepola U, Koponen H, Mehtonen OP, Rimon R: Long-term efficacy and safety of milnacipran compared to clomipramine in patients with major depression. Acta Psychiatr Scand. 1997 Dec;96(6):497-504. Pubmed
• Papakostas GI, Fava M: A meta-analysis of clinical trials comparing milnacipran, a serotonin--norepinephrine reuptake inhibitor, with a selective serotonin reuptake inhibitor for the treatment of major depressive disorder. Eur Neuropsychopharmacol. 2007 Jan;17(1):32-6. Epub 2006 Jun 8. Pubmed
• Kako Y, Niwa Y, Toyomaki A, Yamanaka H, Kitagawa N, Denda K, Koyama T: A case of adult attention-deficit/hyperactivity disorder alleviated by milnacipran. Prog Neuropsychopharmacol Biol Psychiatry. 2007 Apr 13;31(3):772-5. Epub 2007 Jan 12. Pubmed