Darifenacin (BioDeep_00000033239)

   

human metabolite blood metabolite


代谢物信息卡片


2-[(3S)-1-[2-(2,3-dihydro-1-benzofuran-5-yl)ethyl]pyrrolidin-3-yl]-2,2-diphenylacetamide

化学式: C28H30N2O2 (426.2307)
中文名称: 达非那新
谱图信息: 最多检出来源 Homo sapiens(blood) 78.02%

分子结构信息

SMILES: C1CN(CC1C(C2=CC=CC=C2)(C3=CC=CC=C3)C(=O)N)CCC4=CC5=C(C=C4)OCC5
InChI: InChI=1S/C28H30N2O2/c29-27(31)28(23-7-3-1-4-8-23,24-9-5-2-6-10-24)25-14-17-30(20-25)16-13-21-11-12-26-22(19-21)15-18-32-26/h1-12,19,25H,13-18,20H2,(H2,29,31)/t25-/m1/s1

描述信息

G - Genito urinary system and sex hormones > G04 - Urologicals > G04B - Urologicals > G04BD - Drugs for urinary frequency and incontinence
C78272 - Agent Affecting Nervous System > C66880 - Anticholinergic Agent > C29704 - Antimuscarinic Agent
D018377 - Neurotransmitter Agents > D018678 - Cholinergic Agents > D018680 - Cholinergic Antagonists
Darifenacin (Enablex, Novartis) is a medication used to treat urinary incontinence.
C78272 - Agent Affecting Nervous System > C29698 - Antispasmodic Agent
D000089162 - Genitourinary Agents > D064804 - Urological Agents
Darifenacin(UK88525) is a selective M3 muscarinic receptor antagonist with pKi of 8.9. IC50 value: 8.9 (pKi) [1] Target: M3 receptor in vitro: Darifenacin exerts non-parallel rightward displacement of the agonist curve and also significant depression of the maximum response (+)-cis-Dioxolane produced concentration-dependent contraction of the isolated bladder of rat [1]. Darifenacin produces a concentration dependent increase in R123 (P-gp probe) accumulation in MDCK cells. Darifenacin stimulates ATPase activity in P-gp membrane in a clear concentration dependent response manner with an estimated ED50 value of 1.6 μM. Darifenacin (100 nM) shows a significantly greater permeability for darifenacin in the basolateral to apical direction resulting in an efflux ratio in BBMEC monolayers of approximately 2.6 [2]. in vivo: Darifenacin produces dose-dependent inhibition of amplitude of volume-induced bladder contractions(VIBCAMP), producing 35\% inhibition at dose of 283.3 nmol/kg and maximal inhibition of approximately 50–55\% [1]. Darifenacin (0.1 mg/kg i.v.) reduces bladder afferent activity in both Aδ and C fibers in female Sprague-Dawley rats, the decrease in afferent spikes in C fibers may be more pronounced than that in Aδ fibers [3].

同义名列表

12 个代谢物同义名

2-[(3S)-1-[2-(2,3-dihydro-1-benzofuran-5-yl)ethyl]pyrrolidin-3-yl]-2,2-diphenylacetamide; (S)-1-(2-(2,3-Dihydro-5-benzofuranyl)ethyl)-alpha,alpha-diphenyl-3-pyrrolidineacetamide; (S)-1-(2-(2,3-Dihydro-5-benzofuranyl)ethyl)-a,a-diphenyl-3-pyrrolidineacetamide; (S)-1-(2-(2,3-Dihydro-5-benzofuranyl)ethyl)-α,α-diphenyl-3-pyrrolidineacetamide; Darifenacin hydrochloride; Darifenacin hydrobromide; Darifenacine; Darifenacin; Darifenicin; Emselex; Enablex; UK-88525



数据库引用编号

9 个数据库交叉引用编号

分类词条

相关代谢途径

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代谢反应

0 个相关的代谢反应过程信息。

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1 个相关的物种来源信息

在这里通过桑基图来展示出与当前的这个代谢物在我们的BioDeep知识库中具有相关联信息的其他代谢物。在这里进行关联的信息来源主要有：

  • PubMed: 来源于PubMed文献库中的文献信息，我们通过自然语言数据挖掘得到的在同一篇文献中被同时提及的相关代谢物列表，这个列表按照代谢物同时出现的文献数量降序排序，取前10个代谢物作为相关研究中关联性很高的代谢物集合展示在桑基图中。
  • NCBI Taxonomy: 通过文献数据挖掘，得到的代谢物物种来源信息关联。这个关联信息同样按照出现的次数降序排序，取前10个代谢物作为高关联度的代谢物集合展示在桑吉图上。
  • Chemical Taxonomy: 在物质分类上处于同一个分类集合中的其他代谢物
  • Chemical Reaction: 在化学反应过程中，存在为当前代谢物相关联的生化反应过程中的反应底物或者反应产物的关联代谢物信息。

点击图上的相关代谢物的名称，可以跳转到相关代谢物的信息页面。



文献列表

  • Xuelin Zhou, Wai Ping Lam, Hong Chai Tang, Chi-Man Koon, Ling Cheng, Clara Bik-San Lau, Willmann Liang, Ping-Chung Leung. Effects of Gegen (Puerariae lobatae Radix) water extract on improving detrusor overactivity in spontaneously hypertensive rats. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2016 Jun; 23(6):672-8. doi: 10.1016/j.phymed.2016.03.002. [PMID: 27161408]
  • M M Hefnawy, A M Alanazi, M A Abounassif, M S Mohammed, Sabry M Attia, G A E Mostafa. Validated liquid chromatographic-fluorescence method for the quantitation of darifenacin in mice plasma and its application to a pharmacokinetic study. Talanta. 2014 Apr; 121(?):37-42. doi: 10.1016/j.talanta.2013.10.037. [PMID: 24607107]
  • Cho-Ming Loi, Dennis A Smith, Deepak Dalvie. Which metabolites circulate?. Drug metabolism and disposition: the biological fate of chemicals. 2013 May; 41(5):933-51. doi: 10.1124/dmd.112.050278. [PMID: 23454828]
  • Donald W Miller, Martha Hinton, Fang Chen. Evaluation of drug efflux transporter liabilities of darifenacin in cell culture models of the blood-brain and blood-ocular barriers. Neurourology and urodynamics. 2011 Nov; 30(8):1633-8. doi: 10.1002/nau.21110. [PMID: 21826715]
  • Ernesto Callegari, Bimal Malhotra, Peter J Bungay, Rob Webster, Katherine S Fenner, Sarah Kempshall, Jennifer L LaPerle, Martin C Michel, Gary G Kay. A comprehensive non-clinical evaluation of the CNS penetration potential of antimuscarinic agents for the treatment of overactive bladder. British journal of clinical pharmacology. 2011 Aug; 72(2):235-46. doi: 10.1111/j.1365-2125.2011.03961.x. [PMID: 21392072]
  • JianYe Yuan, JiYan Zhou, ZhiBi Hu, Guang Ji, JianQun Xie, DaZheng Wu. The effects of jatrorrhizine on contractile responses of rat ileum. European journal of pharmacology. 2011 Aug; 663(1-3):74-9. doi: 10.1016/j.ejphar.2011.05.002. [PMID: 21596029]
  • Stine Mjåvatn Jakobsen, Hege Kersten, Espen Molden. Evaluation of brain anticholinergic activities of urinary spasmolytic drugs using a high-throughput radio receptor bioassay. Journal of the American Geriatrics Society. 2011 Mar; 59(3):501-5. doi: 10.1111/j.1532-5415.2010.03307.x. [PMID: 21391941]
  • Yun Rose Li, Hiroaki Matsunami. Activation state of the M3 muscarinic acetylcholine receptor modulates mammalian odorant receptor signaling. Science signaling. 2011 Jan; 4(155):ra1. doi: 10.1126/scisignal.2001230. [PMID: 21224444]
  • Manoj K Poonia, Ginpreet Kaur, Meena Chintamaneni, Ilesh Changela. New insights into molecular targets for urinary incontinence. Indian journal of pharmacology. 2010 Oct; 42(5):261-6. doi: 10.4103/0253-7613.69980. [PMID: 21206614]
  • Gerald P McCafferty, Robert W Coatney, Nicholas J Laping, Kevin S Thorneloe. Urodynamic measurements by radiotelemetry in conscious, freely moving beagle dogs. The Journal of urology. 2009 Mar; 181(3):1444-51. doi: 10.1016/j.juro.2008.10.137. [PMID: 19157444]
  • Lambertus P W Witte, Wilhemina M C Mulder, Jean J M C H de la Rosette, Martin C Michel. Muscarinic receptor antagonists for overactive bladder treatment: does one fit all?. Current opinion in urology. 2009 Jan; 19(1):13-9. doi: 10.1097/mou.0b013e32831a6ff3. [PMID: 19057211]
  • Yao-Chi Chuang, Catherine A Thomas, Shachi Tyagi, Naoki Yoshimura, Pradeep Tyagi, Michael B Chancellor. Human urine with solifenacin intake but not tolterodine or darifenacin intake blocks detrusor overactivity. International urogynecology journal and pelvic floor dysfunction. 2008 Oct; 19(10):1353-7. doi: 10.1007/s00192-008-0650-7. [PMID: 18504514]
  • Martin C Michel, Sergio Parra. Similarities and differences in the autonomic control of airway and urinary bladder smooth muscle. Naunyn-Schmiedeberg's archives of pharmacology. 2008 Aug; 378(2):217-24. doi: 10.1007/s00210-008-0316-5. [PMID: 18548230]
  • R Scott Obach, Franco Lombardo, Nigel J Waters. Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds. Drug metabolism and disposition: the biological fate of chemicals. 2008 Jul; 36(7):1385-405. doi: 10.1124/dmd.108.020479. [PMID: 18426954]
  • Myeong Heon Jin, Du Geon Moon. Practical management of nocturia in urology. Indian journal of urology : IJU : journal of the Urological Society of India. 2008 Jul; 24(3):289-94. doi: 10.4103/0970-1591.42607. [PMID: 19468456]
  • Elfaridah P Frazier, Stephan L M Peters, Alan S Braverman, Michael R Ruggieri, Martin C Michel. Signal transduction underlying the control of urinary bladder smooth muscle tone by muscarinic receptors and beta-adrenoceptors. Naunyn-Schmiedeberg's archives of pharmacology. 2008 Jun; 377(4-6):449-62. doi: 10.1007/s00210-007-0208-0. [PMID: 18060543]
  • Jean-Jacques Wyndaele, Stefan De Wachter. Urgency in overactive bladder: translating experimental data into clinical practice. Drugs of today (Barcelona, Spain : 1998). 2008 May; 44(5):381-9. doi: 10.1358/dot.2008.44.5.1215723. [PMID: 18548139]
  • Kristen Hesch. Agents for treatment of overactive bladder: a therapeutic class review. Proceedings (Baylor University. Medical Center). 2007 Jul; 20(3):307-14. doi: 10.1080/08998280.2007.11928310. [PMID: 17637888]
  • Scott A MacDiarmid. Maximizing anticholinergic therapy for overactive bladder: has the ceiling been reached?. BJU international. 2007 Jun; 99 Suppl 3(?):8-12. doi: 10.1111/j.1464-410x.2007.06881.x. [PMID: 17488367]
  • M Goepel, K-C Steinwachs. [How do medications used to treat urinary incontinence affect the cerebral function of the elderly?]. Der Urologe. Ausg. A. 2007 Apr; 46(4):387-8, 390. doi: 10.1007/s00120-007-1326-5. [PMID: 17377763]
  • Jane Miller, Eileen Hoffman. The causes and consequences of overactive bladder. Journal of women's health (2002). 2006 Apr; 15(3):251-60. doi: 10.1089/jwh.2006.15.251. [PMID: 16620184]
  • Nurum Erdem, Franklin M Chu. Management of overactive bladder and urge urinary incontinence in the elderly patient. The American journal of medicine. 2006 Mar; 119(3 Suppl 1):29-36. doi: 10.1016/j.amjmed.2005.12.014. [PMID: 16483866]
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  • Sharath S Hegde. Muscarinic receptors in the bladder: from basic research to therapeutics. British journal of pharmacology. 2006 Feb; 147 Suppl 2(?):S80-7. doi: 10.1038/sj.bjp.0706560. [PMID: 16465186]
  • Andrej Skerjanec. The clinical pharmacokinetics of darifenacin. Clinical pharmacokinetics. 2006; 45(4):325-50. doi: 10.2165/00003088-200645040-00001. [PMID: 16584282]
  • David Rp Guay. Trospium chloride: an update on a quaternary anticholinergic for treatment of urge urinary incontinence. Therapeutics and clinical risk management. 2005 Jun; 1(2):157-67. doi: 10.2147/tcrm.1.2.157.62912. [PMID: 18360555]
  • David R Staskin. Overactive bladder in the elderly: a guide to pharmacological management. Drugs & aging. 2005; 22(12):1013-28. doi: 10.2165/00002512-200522120-00003. [PMID: 16363885]
  • Mitchell R Humphreys, Yuri E Reinberg. Contemporary and emerging drug treatments for urinary incontinence in children. Paediatric drugs. 2005; 7(3):151-62. doi: 10.2165/00148581-200507030-00002. [PMID: 15977961]
  • Rien J M Nijman. Role of antimuscarinics in the treatment of nonneurogenic daytime urinary incontinence in children. Urology. 2004 Mar; 63(3 Suppl 1):45-50. doi: 10.1016/j.urology.2003.11.004. [PMID: 15013652]
  • Thomas Kerbusch, Ulrika Wählby, Peter A Milligan, Mats O Karlsson. Population pharmacokinetic modelling of darifenacin and its hydroxylated metabolite using pooled data, incorporating saturable first-pass metabolism, CYP2D6 genotype and formulation-dependent bioavailability. British journal of clinical pharmacology. 2003 Dec; 56(6):639-52. doi: 10.1046/j.1365-2125.2003.01967.x. [PMID: 14616424]
  • H Hirose, I Aoki, T Kimura, T Fujikawa, T Numazawa, K Sasaki, A Sato, T Hasegawa, M Nishikibe, M Mitsuya, N Ohtake, T Mase, K Noguchi. Pharmacological properties of (2R)-N-[1-(6-aminopyridin-2-ylmethyl)piperidin-4-yl]-2-[(1R)-3,3-difluorocyclopentyl]-2-hydroxy-2-phenylacetamide: a novel mucarinic antagonist with M(2)-sparing antagonistic activity. The Journal of pharmacology and experimental therapeutics. 2001 May; 297(2):790-7. doi: NULL. [PMID: 11303071]
  • K C Beaumont, N J Cussans, D J Nichols, D A Smith. Pharmacokinetics and metabolism of darifenacin in the mouse, rat, dog and man. Xenobiotica; the fate of foreign compounds in biological systems. 1998 Jan; 28(1):63-75. doi: 10.1080/004982598239768. [PMID: 9493320]
  • B Kaye, W J Herron, P V Macrae, S Robinson, D A Stopher, R F Venn, W Wild. Rapid, solid phase extraction technique for the high-throughput assay of darifenacin in human plasma. Analytical chemistry. 1996 May; 68(9):1658-60. doi: 10.1021/ac9507552. [PMID: 8815750]