Darifenacin

Darifenacin
Clinical data
Trade names	Enablex, Emselex
AHFS/Drugs.com	Monograph
MedlinePlus	a605039
Pregnancy; category	AU: B3; ;
Routes of; administration	By mouth
ATC code	G04BD10 (WHO) ;
Legal status
Legal status	AU: S4 (Prescription only); UK: POM (Prescription only); US: ℞-only; EU: Rx-only;
Pharmacokinetic data
Bioavailability	15 to 19% (dose-dependent)
Protein binding	98%
Metabolism	Liver (CYP2D6- and CYP3A4-mediated)
Elimination half-life	13 to 19 hours
Excretion	Kidney (60%) and biliary (40%)
Identifiers
	IUPAC name (S)-2-[1-[2-(2,3-dihydrobenzofuran-5-yl)ethyl] pyrrolidin-3-yl] -2,2-diphenyl-acetamide;
CAS Number	133099-04-4 ;
PubChem CID	444031;
IUPHAR/BPS	321;
DrugBank	DB00496 ;
ChemSpider	392054 ;
UNII	APG9819VLM;
KEGG	D03654 ; as salt: D01699 ;
ChEBI	CHEBI:391960 ;
ChEMBL	ChEMBL1346 ;
CompTox Dashboard (EPA)	DTXSID2048290 ;
ECHA InfoCard	100.118.382
Chemical and physical data
Formula	C28H30N2O2
Molar mass	426.560 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O=C(N)C(c1ccccc1)(c2ccccc2)[C@H]3CN(CC3)CCc5cc4c(OCC4)cc5;
	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 ; Key:HXGBXQDTNZMWGS-RUZDIDTESA-N ;
	(what is this?) (verify)

Darifenacin (trade name Enablex in United States and Canada, Emselex in the European Union) is a medication used to treat urinary incontinence due to an overactive bladder.^[1]^[2]^[3] It was discovered by scientists at the Pfizer research site in Sandwich, UK under the identifier UK-88,525 and used to be marketed by Novartis. In 2010, the US rights were sold to Warner Chilcott for US$400 million.

Adverse effects

Darifenacin should not be used in people with urinary retention. Anticholinergic agents, such as darifenacin, may also produce constipation and blurred vision. Heat prostration (due to decreased sweating) can occur when anticholinergics such as darifenacin are used in a hot environment.^[4]

Medical uses

Darifenacin is indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency and frequency in adults. It may also be recommended with an alpha blocker to help provide symptomatic benefit for overactive bladder and obstructive symptoms such as likely associated with benign prostatic hypertrophy. ^[5]

Mechanism of action

Darifenacin works by blocking the M₃ muscarinic acetylcholine receptor, which is primarily responsible for bladder muscle contractions. It thereby decreases the urgency to urinate.^[6] It is not known whether this selectivity for the M₃ receptor translates into any clinical advantage when treating symptoms of overactive bladder syndrome.^[4] Although it is said to be selective for the M₃ receptor, darifenacin is also said to antagonize the other four muscarinic acetylcholine receptors.^[7]

References

^ Croom KF, Keating GM (2004). "Darifenacin: in the treatment of overactive bladder". Drugs & Aging. 21 (13): 885–92, discussion 893–4. doi:10.2165/00002512-200421130-00005. PMID 15493952. S2CID 41549419.
^ Parsons M, Robinson D, Cardozo L (July 2005). "Darifenacin in the treatment of overactive bladder". International Journal of Clinical Practice. 59 (7): 831–8. doi:10.1111/j.1368-5031.2005.00585.x. PMID 15963212. S2CID 39061659.
^ Chughtai B, Levin R, De E (2008). "Choice of antimuscarinic agents for overactive bladder in the older patient: focus on darifenacin". Clinical Interventions in Aging. 3 (3): 503–9. doi:10.2147/cia.s3414. PMC 2682382. PMID 18982920.
^ ^a ^b "Enablex- darifenacin tablet, extended release". DailyMed. 24 September 2016. Retrieved 22 October 2020.
^ American Urological Association (AUA) Guideline. Diagnosis and Treatment of Overactive Bladder in Adults: AUA/SUFA guideline 2012
^ Chapple CR (November 2004). "Darifenacin: a novel M3 muscarinic selective receptor antagonist for the treatment of overactive bladder". Expert Opinion on Investigational Drugs. 13 (11): 1493–500. doi:10.1517/13543784.13.11.1493. PMID 15500396. S2CID 19259076.
^ Lavrador M, Cabral AC, Veríssimo MT, Fernandez-Llimos F, Figueiredo IV, Castel-Branco MM (January 2023). "A Universal Pharmacological-Based List of Drugs with Anticholinergic Activity". Pharmaceutics. 15 (1): 230. doi:10.3390/pharmaceutics15010230. PMC 9863833. PMID 36678858.

External links

"Darifenacin". Drug Information Portal. U.S. National Library of Medicine.
"Darifenacin hydrobromide". Drug Information Portal. U.S. National Library of Medicine.

[Croom_2004-1] Croom KF, Keating GM (2004). "Darifenacin: in the treatment of overactive bladder". Drugs & Aging. 21 (13): 885–92, discussion 893–4. doi:10.2165/00002512-200421130-00005. PMID 15493952. S2CID 41549419.

[Parsons_2005-2] Parsons M, Robinson D, Cardozo L (July 2005). "Darifenacin in the treatment of overactive bladder". International Journal of Clinical Practice. 59 (7): 831–8. doi:10.1111/j.1368-5031.2005.00585.x. PMID 15963212. S2CID 39061659.

[Chughtai_2008-3] Chughtai B, Levin R, De E (2008). "Choice of antimuscarinic agents for overactive bladder in the older patient: focus on darifenacin". Clinical Interventions in Aging. 3 (3): 503–9. doi:10.2147/cia.s3414. PMC 2682382. PMID 18982920.

[Enablex_FDA_label-4] "Enablex- darifenacin tablet, extended release". DailyMed. 24 September 2016. Retrieved 22 October 2020.

[5] American Urological Association (AUA) Guideline. Diagnosis and Treatment of Overactive Bladder in Adults: AUA/SUFA guideline 2012

[Chapple_2004-6] Chapple CR (November 2004). "Darifenacin: a novel M3 muscarinic selective receptor antagonist for the treatment of overactive bladder". Expert Opinion on Investigational Drugs. 13 (11): 1493–500. doi:10.1517/13543784.13.11.1493. PMID 15500396. S2CID 19259076.

[LavradorCabralVeríssimo2023-7] Lavrador M, Cabral AC, Veríssimo MT, Fernandez-Llimos F, Figueiredo IV, Castel-Branco MM (January 2023). "A Universal Pharmacological-Based List of Drugs with Anticholinergic Activity". Pharmaceutics. 15 (1): 230. doi:10.3390/pharmaceutics15010230. PMC 9863833. PMID 36678858.

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