Darifenacin HBr | UK-88525 | 133099-07-7 | M3 muscarinic acetylcholine receptor

MedKoo Cat#: 317583 | Name: Darifenacin HBr

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Darifenacin, also known as UK-88525, is a medication used to treat urinary incontinence. Darifenacin works by blocking the M3 muscarinic acetylcholine receptor, which is primarily responsible for bladder muscle contractions. It thereby decreases the urgency to urinate.

Chemical Structure

Darifenacin HBr

CAS#133099-07-7 (HBr)

Theoretical Analysis

MedKoo Cat#: 317583

Name: Darifenacin HBr

CAS#: 133099-07-7 (HBr)

Chemical Formula: C28H31BrN2O

Exact Mass: 426.2307

Molecular Weight: 507.47

Elemental Analysis: C, 66.27; H, 6.16; Br, 15.75; N, 5.52; O, 6.31

Price and Availability

Size	Price	Availability
1g	USD 250.00	2 Weeks
5g	USD 450.00	2 Weeks
10g	USD 950.00	2 Weeks

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Related CAS #

133099-04-4 (free base) 133099-07-7 (HBr)

Synonym

UK-88525-04; UK 88525-04; UK88525-04; Darifenacin; Emselex; Enablex. Darifenacin HBr; Darilong

IUPAC/Chemical Name

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

InChi Key

UQAVIASOPREUIT-VQIWEWKSSA-N

InChi Code

InChI=1S/C28H30N2O2.BrH/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);1H/t25-;/m1./s1

SMILES Code

O=C(N)C(C1=CC=CC=C1)([C@H]2CN(CCC3=CC4=C(OCC4)C=C3)CC2)C5=CC=CC=C5.[H]Br

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#A20K08S05

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Darifenacin hydrobromide (UK-88525 hydrobromide) is a selective M3 muscarinic receptor antagonist with pKi of 8.9.

In vitro activity:

Darifenacin, an anticholinergic agent, has been used to treat overactive bladder syndrome. Despite its extensive clinical use, there is little information about the effect of darifenacin on vascular ion channels, specifically K+ channels. This study aimed to investigate the effect of the anti-muscarinic drug darifenacin on voltage-gated K+ (Kv) channels, vascular contractility, and coronary blood flow in rabbit coronary arteries. Isometric organ bath experiments using isolated coronary arteries were applied to evaluate whether darifenacin-induced inhibition of the Kv channel causes vasocontraction. Darifenacin substantially induced vasocontraction. Furthermore, darifenacin caused membrane depolarization and decreased coronary blood flow. From these results, it is concluded that darifenacin inhibits the Kv currents in concentration- and use- (state)-dependent manners. Inhibition of the Kv current with darifenacin occurred by shifting the steady-state activation and inactivation curves regardless of its anti-muscarinic effect. Reference: Eur J Pharmacol. 2021 Jan 15;891:173707. https://pubmed.ncbi.nlm.nih.gov/33137332/

In vivo activity:

A novel muscarinic receptor antagonist, darifenacin, inhibited specific binding of [N-methyl-(3)H]scopolamine ([(3)H]NMS) in the mouse bladder, submaxillary gland and heart in a concentration-dependent manner. The inhibitory effect was most potent in the submaxillary gland, followed by the bladder and heart. At 0.5 to 12 h after oral administration of darifenacin, a significant increase in K(d) values for specific [(3)H]NMS binding was seen in the bladder, submaxillary gland and lung of mice, compared with control values. Also, there was a sustained decrease in the B(max) values in the submaxillary gland. These data suggest that muscarinic receptor binding of oral darifenacin is rapid in onset and of a long duration. On the other hand, oral darifenacin exerted only temporary or little binding of muscarinic receptors in the heart and colon. Pilocarpine-induced salivary secretion in mice was continuously suppressed by oral darifenacin. The time-course of suppression coincided well with that for the muscarinic receptor binding in the submaxillary gland. The antagonistic effect of darifenacin against the dose-response curves for pilocarpine appeared to be insurmountable. In conclusion, the present study has shown that oral darifenacin may exert a pronounced and long-lasting binding of muscarinic receptors in tissues expressing the M(3) subtype. Reference: Life Sci. 2006 Dec 14;80(2):127-32. https://pubmed.ncbi.nlm.nih.gov/16996089/

	Solvent	mg/mL	mM
Solubility
	DMSO	45.0	88.67

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 507.47 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Seo MS, An JR, Jung HS, Kang M, Heo R, Han ET, Yang SR, Park H, Jung WK, Choi IW, Bae YM, Na SH, Park WS. Suppression of voltage-gated K+ channels by darifenacin in coronary arterial smooth muscle cells. Eur J Pharmacol. 2021 Jan 15;891:173707. doi: 10.1016/j.ejphar.2020.173707. Epub 2020 Oct 31. PMID: 33137332. 2. Iijima K, De Wachter S, Wyndaele JJ. Effects of the M3 receptor selective muscarinic antagonist darifenacin on bladder afferent activity of the rat pelvic nerve. Eur Urol. 2007 Sep;52(3):842-7. doi: 10.1016/j.eururo.2007.02.057. Epub 2007 Mar 6. PMID: 17360104. 3. Yamada S, Maruyama S, Takagi Y, Uchida S, Oki T. In vivo demonstration of M3 muscarinic receptor subtype selectivity of darifenacin in mice. Life Sci. 2006 Dec 14;80(2):127-32. doi: 10.1016/j.lfs.2006.08.028. Epub 2006 Sep 1. PMID: 16996089.

In vitro protocol:

In vivo protocol:

1: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012–. Darifenacin. 2023 Jul 12. PMID: 31644105. 2: Croom KF, Keating GM. Darifenacin: in the treatment of overactive bladder. Drugs Aging. 2004;21(13):885-92; discussion 893-4. doi: 10.2165/00002512-200421130-00005. PMID: 15493952. 3: Steers WD. Darifenacin: Pharmacology and clinical usage. Urol Clin North Am. 2006 Nov;33(4):475-82, viii. doi: 10.1016/j.ucl.2006.06.007. PMID: 17011383. 4: Haab F. Darifenacin in the treatment of overactive bladder. Drugs Today (Barc). 2005 Jul;41(7):441-52. doi: 10.1358/dot.2005.41.7.891719. PMID: 16193097. 5: Haab F, Stewart L, Dwyer P. Darifenacin, an M3 selective receptor antagonist, is an effective and well-tolerated once-daily treatment for overactive bladder. Eur Urol. 2004 Apr;45(4):420-9; discussion 429. doi: 10.1016/j.eururo.2004.01.008. PMID: 15041104. 6: Parsons M, Robinson D, Cardozo L. Darifenacin in the treatment of overactive bladder. Int J Clin Pract. 2005 Jul;59(7):831-8. doi: 10.1111/j.1368-5031.2005.00585.x. PMID: 15963212. 7: Skerjanec A. The clinical pharmacokinetics of darifenacin. Clin Pharmacokinet. 2006;45(4):325-50. doi: 10.2165/00003088-200645040-00001. PMID: 16584282. 8: Zinner N. Darifenacin: a muscarinic M3-selective receptor antagonist for the treatment of overactive bladder. Expert Opin Pharmacother. 2007 Mar;8(4):511-23. doi: 10.1517/14656566.8.4.511. PMID: 17309345. 9: Selvanayagam S, Sridhar B, Ravikumar K. Darifenacin hydro-bromide. Acta Crystallogr Sect E Struct Rep Online. 2009 May 14;65(Pt 6):o1286. doi: 10.1107/S1600536809017085. PMID: 21583148; PMCID: PMC2969553. 10: Nie M, Chen N, Pang H, Jiang T, Jiang W, Tian P, Yao L, Chen Y, DeBerardinis RJ, Li W, Yu Q, Zhou C, Hu Z. Targeting acetylcholine signaling modulates persistent drug tolerance in EGFR-mutant lung cancer and impedes tumor relapse. J Clin Invest. 2022 Oct 17;132(20):e160152. doi: 10.1172/JCI160152. PMID: 36048538; PMCID: PMC9566900. 11: Chapple CR. Darifenacin: a novel M3 muscarinic selective receptor antagonist for the treatment of overactive bladder. Expert Opin Investig Drugs. 2004 Nov;13(11):1493-500. doi: 10.1517/13543784.13.11.1493. PMID: 15500396. 12: Guay DR. Darifenacin: another antimuscarinic for overactive bladder. Consult Pharm. 2005 May;20(5):424-31. doi: 10.4140/tcp.n.2005.424. PMID: 16548640. 13: Seo MS, An JR, Jung HS, Kang M, Heo R, Han ET, Yang SR, Park H, Jung WK, Choi IW, Bae YM, Na SH, Park WS. Suppression of voltage-gated K+ channels by darifenacin in coronary arterial smooth muscle cells. Eur J Pharmacol. 2021 Jan 15;891:173707. doi: 10.1016/j.ejphar.2020.173707. Epub 2020 Oct 31. PMID: 33137332. 14: Chughtai B, Levin R, De E. Choice of antimuscarinic agents for overactive bladder in the older patient: focus on darifenacin. Clin Interv Aging. 2008;3(3):503-9. doi: 10.2147/cia.s3414. PMID: 18982920; PMCID: PMC2682382. 15: Welk B, Richardson K, Panicker JN. The cognitive effect of anticholinergics for patients with overactive bladder. Nat Rev Urol. 2021 Nov;18(11):686-700. doi: 10.1038/s41585-021-00504-x. Epub 2021 Aug 24. PMID: 34429535. 16: Kay GG, Ebinger U. Preserving cognitive function for patients with overactive bladder: evidence for a differential effect with darifenacin. Int J Clin Pract. 2008 Nov;62(11):1792-800. doi: 10.1111/j.1742-1241.2008.01849.x. Epub 2008 Aug 11. PMID: 18699842; PMCID: PMC2734922. 17: McFerren SC, Gomelsky A. Treatment of Overactive Bladder in the Elderly Female: The Case for Trospium, Oxybutynin, Fesoterodine and Darifenacin. Drugs Aging. 2015 Oct;32(10):809-19. doi: 10.1007/s40266-015-0301-x. PMID: 26391900. 18: Kershen RT, Hsieh M. Preview of new drugs for overactive bladder and incontinence: darifenacin, solifenacin, trospium, and duloxetine. Curr Urol Rep. 2004 Oct;5(5):359-67. doi: 10.1007/s11934-004-0083-x. PMID: 15461912. 19: Jha S, Parsons M. Treatment of overactive bladder in the aging population: focus on darifenacin. Clin Interv Aging. 2006;1(4):309-16. doi: 10.2147/ciia.2006.1.4.309. PMID: 18046909; PMCID: PMC2699645. 20: Kissane LM, Martin KD, Meyer I, Richter HE. Effect of darifenacin on fecal incontinence in women with double incontinence. Int Urogynecol J. 2021 Sep;32(9):2357-2363. doi: 10.1007/s00192-020-04369-3. Epub 2020 Jun 15. PMID: 32542466; PMCID: PMC7736065.