(9R)-10-methyl-10-azatetracyclo[7.7.1.0^{2,7}.0^{13,17}]heptadeca-1(16),2(7),3,5,13(17),14-hexaene-3,4-diol

• ChemBase编号: 595
• 分子式: C17H17NO2
• 平均质量: 267.32238
• 单一同位素质量: 267.12592879
• SMILES: Oc1c2c3c4[C@H](N(CCc4ccc3)C)Cc2ccc1O
• Canonical SMILES: CN1CCc2c3[C@H]1Cc1ccc(c(c1c3ccc2)O)O
• InChI: InChI=1S/C17H17NO2/c1-18-8-7-10-3-2-4-12-15(10)13(18)9-11-5-6-14(19)17(20)16(11)12/h2-6,13,19-20H,7-9H2,1H3/t13-/m1/s1
• InChIKey: VMWNQDUVQKEIOC-CYBMUJFWSA-N

名称和登记号

名称

• IUPAC标准名: (9R)-10-methyl-10-azatetracyclo[7.7.1.0^{2,7}.0^{13,17}]heptadeca-1(16),2(7),3,5,13(17),14-hexaene-3,4-diol; (9R)-10-methyl-10-azatetracyclo[7.7.1.0^2,^7.0^1^3,^1^7]heptadeca-1(17),2,4,6,13,15-hexaene-3,4-diol
• IUPAC传统名: apomorphine
• 商标名: Uprima; Ixense; Apokyn
• 别名: Apomorfin; Apomorphine Hydrochloride Hemihydrate; Apomorphinium Chloride Hemihydrate; Apormorphine; L-Apomorphine; apomorphine; VR004; VR-040; VR-400; Apomorphine Hydrochloride; Apomorphine

登记号

• CAS号: 41372-20-7
• PubChem SID: 160964058; 46508653
• PubChem CID: 6005
• CHEBI ID: 48538
• ATC码: N04BC07; G04BE07
• CHEMBL: 53
• Chemspider ID: 5783
• DrugBank ID: DB00714
• IUPHAR配体索引: 33
• KEGG ID: D07460
• 美国药典/FDA物质标识码: F39049Y068
• 维基百科标题: Apomorphine
• Medline Plus: a604020

理论计算性质

JChem

• Acid pKa: 6.5761385
• 质子受体: 3
• 质子供体: 2
• LogD (pH = 5.5): 0.9807055
• LogD (pH = 7.4): 2.013494
• Log P: 2.054109
• 摩尔折射率: 79.9881 cm^3
• 极化性: 31.638338 Å^3
• 极化表面积: 43.7 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: 2.51
• LOG S: -2.72
• 溶解度: 5.10e-01 g/l

分子性质

理化性质

• 溶解度: 1.66E+004 mg/L
• 疏水性(logP): 3.1

药理学性质

• 给药途径: Oral, SC
• 生物利用度: 100% following sc injection
• 半衰期: 40 minutes (range 30-60 minutes)
• 代谢: Hepatic
• 蛋白结合率: ~50%
• 法定药品分级: Rx-only
• 妊娠期药物分类: C

详细说明

DrugBank - DB00714

• Drug Groups: approved; investigational
• Description: A derivative of morphine that is a dopamine D2 agonist. It is a powerful emetic and has been used for that effect in acute poisoning. It has also been used in the diagnosis and treatment of parkinsonism, but its adverse effects limit its use. [PubChem]
• Indication: For the acute, intermittent treatment of hypomobility, off episodes (end-of-dose wearing off and unpredictable on/off episodes) associated with advanced Parkinson's disease.
• Pharmacology: Apomorphine is a type of dopaminergic agonist, a morphine derivative which primarily affects the hypothalamic region of the brain. Drugs containing this substance are sometimes used in the treatment of Parkinson's disease or erectile dysfunction. In higher doses it is a highly effective emetic.
• Toxicity: LD₅₀=0.6 mmoles/kg (mice, intraperitoneal)
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic
• Absorption: 100% following subcutaneous administration
• Half Life: 40 minutes (range 30 - 60 minutes)
• Protein Binding: ~50%-albumin
• Distribution: * 123 to 404 L
• Clearance: * 223 L/hr
• References: Matsumoto K, Yoshida M, Andersson KE, Hedlund P: Effects in vitro and in vivo by apomorphine in the rat corpus cavernosum. Br J Pharmacol. 2005 Sep;146(2):259-67. [Pubmed] ; SCHWAB RS, AMADOR LV, LETTVIN JY: Apomorphine in Parkinson's disease. Trans Am Neurol Assoc. 1951;56:251-3. [Pubmed] ; Cotzias GC, Papavasiliou PS, Fehling C, Kaufman B, Mena I: Similarities between neurologic effects of L-dipa and of apomorphine. N Engl J Med. 1970 Jan 1;282(1):31-3. [Pubmed] ; Corsini GU, Del Zompo M, Gessa GL, Mangoni A: Therapeutic efficacy of apomorphine combined with an extracerebral inhibitor of dopamine receptors in Parkinson's disease. Lancet. 1979 May 5;1(8123):954-6. [Pubmed] ; Chaudhuri KR, Clough C: Subcutaneous apomorphine in Parkinson's disease. BMJ. 1998 Feb 28;316(7132):641. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

参考文献

• Matsumoto K, Yoshida M, Andersson KE, Hedlund P: Effects in vitro and in vivo by apomorphine in the rat corpus cavernosum. Br J Pharmacol. 2005 Sep;146(2):259-67. Pubmed
• SCHWAB RS, AMADOR LV, LETTVIN JY: Apomorphine in Parkinson's disease. Trans Am Neurol Assoc. 1951;56:251-3. Pubmed
• Cotzias GC, Papavasiliou PS, Fehling C, Kaufman B, Mena I: Similarities between neurologic effects of L-dipa and of apomorphine. N Engl J Med. 1970 Jan 1;282(1):31-3. Pubmed
• Corsini GU, Del Zompo M, Gessa GL, Mangoni A: Therapeutic efficacy of apomorphine combined with an extracerebral inhibitor of dopamine receptors in Parkinson's disease. Lancet. 1979 May 5;1(8123):954-6. Pubmed
• Chaudhuri KR, Clough C: Subcutaneous apomorphine in Parkinson's disease. BMJ. 1998 Feb 28;316(7132):641. Pubmed