methyl 2-phenyl-2-(piperidin-2-yl)acetate

• ChemBase编号: 305
• 分子式: C14H19NO2
• 平均质量: 233.30616
• 单一同位素质量: 233.14157885
• SMILES: O(C(=O)C(C1NCCCC1)c1ccccc1)C
• Canonical SMILES: COC(=O)C(c1ccccc1)C1CCCCN1
• InChI: InChI=1S/C14H19NO2/c1-17-14(16)13(11-7-3-2-4-8-11)12-9-5-6-10-15-12/h2-4,7-8,12-13,15H,5-6,9-10H2,1H3
• InChIKey: DUGOZIWVEXMGBE-UHFFFAOYSA-N

名称和登记号

名称

• IUPAC标准名: methyl 2-phenyl-2-(piperidin-2-yl)acetate
• IUPAC传统名: methylphenidate
• 商标名: Ritalin-SR; Ritaline; Ritcher Works; Daytrana; Metadate; Metadate CD; Metadate ER; Methylin; Methylin ER; Methylofenidan; Methylphenidan; Methypatch; Plimasine; PMS-Methylphenidate; Riphenidate; Ritalin; Ritalin hydrochloride; Ritalin LA; Ritalin SR; 4311/B Ciba; Calocain; Centedein; Centedrin; Centedrine; Centredin; Concerta; Focalin; Focalin XR; Methylphen; Meridil; Concerta, Methylin, Ritalin
• 别名: Methyl phenidyl acetate; Methylphenidate HCl; Methylphenidate hydrochloride; Methylphenidatum [INN-Latin]; Methylphenidylacetate hydrochloride; Metilfenidat hydrochloride; Metilfenidato [INN-Spanish]; Metilfenidato [Italian]; Phenidylate; d-methylphenidate HCl; methylphenidate; Methylphenidate

登记号

• CAS号: 113-45-1
• PubChem SID: 160963768; 46505929
• PubChem CID: 4158
• CHEBI ID: 6887
• ATC码: N06BA04
• CHEMBL: 796
• Chemspider ID: 4015
• DrugBank ID: DB00422
• KEGG ID: D04999
• 美国药典/FDA物质标识码: 207ZZ9QZ49
• 维基百科标题: Methylphenidate
• Medline Plus: a682188

理论计算性质

JChem

• 质子受体: 2
• 质子供体: 1
• LogD (pH = 5.5): -0.8258359
• LogD (pH = 7.4): 0.5692904
• Log P: 2.254935
• 摩尔折射率: 66.7282 cm^3
• 极化性: 26.621723 Å^3
• 极化表面积: 38.33 Å^2
• 可自由旋转的化学键: 4
• 里宾斯基五规则: true

ALOGPS 2.1

• Log P: 1.47
• LOG S: -3.11
• 溶解度: 1.82e-01 g/l

分子性质

理化性质

• 溶解度: 1255mg/L
• 熔点: 214°C (417.2°F)
• 疏水性(logP): 2.1

药理学性质

• 给药途径: Oral, Transdermal
• 生物利用度: 11–52%
• 依赖倾向: Moderate
• 排泄: Urine
• 半衰期: Immediate release tablets = 4 hours; extended release capsules = 7-12 hours
• 代谢: Liver (80%)
• 蛋白结合率: 30%
• 法定药品分级: POM (UK); Rx-only; Schedule 8 (Australia); Schedule II (US); Schedule III (Canada)
• 妊娠期药物分类: C
• 美国（FDA）药品许可证: Methylphenidate

详细说明

DrugBank - DB00422

• Drug Groups: approved; investigational
• Description: A central nervous system stimulant used most commonly in the treatment of attention-deficit disorders in children and for narcolepsy. Its mechanisms appear to be similar to those of dextroamphetamine. [PubChem]
• Indication: For use as an integral part of a total treatment program which typically includes other remedial measures (psychological, educational, social) for a stabilizing effect in children with a behavioral syndrome characterized by the following group of developmentally inappropriate symptoms: moderate-to-severe distractibility, short attention span, hyperactivity, emotional lability, and impulsivity.
• Pharmacology: Methylphenidate is a central nervous system stimulant used most commonly in the treatment of attention-deficit disorders in children and for narcolepsy. Its mechanisms appear to be similar to those of dextroamphetamine.
• Toxicity: Symptoms of overdose include vomiting, agitation, tremors, hyperreflexia, muscle twitching, convulsions (may be followed by coma), euphoria, confusion, hallucinations, delirium, sweating, flushing, headache, hyperpyrexia, tachycardia, palpitations, cardiac arrhythmias, hypertension, mydriasis, and dryness of mucous membranes. LD₅₀=190mg/kg (orally in mice)
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic, methylphenidate is metabolized primarily by de-esterification to ritalinic acid (α-phenyl-2-piperidine acetic acid, PPAA), which has little to no pharmacologic activity.
• Absorption: Readily absorbed in a biphasic manner. It reaches peak absorption at approximately two hours for the first phase and five hours for the second phase. Bioavailability is low (approximately 30%)
• Half Life: 2.4 hours in children and 2.1 hours in adults
• Protein Binding: Low (approximately 15%)
• References: Keating GM, McClellan K, Jarvis B: Methylphenidate (OROS formulation). CNS Drugs. 2001;15(6):495-500; discussion 501-3. [Pubmed] ; Markowitz JS, DeVane CL, Pestreich LK, Patrick KS, Muniz R: A comprehensive in vitro screening of d-, l-, and dl-threo-methylphenidate: an exploratory study. J Child Adolesc Psychopharmacol. 2006 Dec;16(6):687-98. [Pubmed] ; Fone KC, Nutt DJ: Stimulants: use and abuse in the treatment of attention deficit hyperactivity disorder. Curr Opin Pharmacol. 2005 Feb;5(1):87-93. [Pubmed] ; Sharma RP, Javaid JI, Pandey GN, Easton M, Davis JM: Pharmacological effects of methylphenidate on plasma homovanillic acid and growth hormone. Psychiatry Res. 1990 Apr;32(1):9-17. [Pubmed] ; Shults T, Kownacki AA, Woods WE, Valentine R, Dougherty J, Tobin T: Pharmacokinetics and behavioral effects of methylphenidate in Thoroughbred horses. Am J Vet Res. 1981 May;42(5):722-6. [Pubmed]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

参考文献

• Keating GM, McClellan K, Jarvis B: Methylphenidate (OROS formulation). CNS Drugs. 2001;15(6):495-500; discussion 501-3. Pubmed
• Markowitz JS, DeVane CL, Pestreich LK, Patrick KS, Muniz R: A comprehensive in vitro screening of d-, l-, and dl-threo-methylphenidate: an exploratory study. J Child Adolesc Psychopharmacol. 2006 Dec;16(6):687-98. Pubmed
• Fone KC, Nutt DJ: Stimulants: use and abuse in the treatment of attention deficit hyperactivity disorder. Curr Opin Pharmacol. 2005 Feb;5(1):87-93. Pubmed
• Sharma RP, Javaid JI, Pandey GN, Easton M, Davis JM: Pharmacological effects of methylphenidate on plasma homovanillic acid and growth hormone. Psychiatry Res. 1990 Apr;32(1):9-17. Pubmed
• Shults T, Kownacki AA, Woods WE, Valentine R, Dougherty J, Tobin T: Pharmacokinetics and behavioral effects of methylphenidate in Thoroughbred horses. Am J Vet Res. 1981 May;42(5):722-6. Pubmed