Mirabegron

Mirabegron

Clinical data
Trade names	Myrbetriq (US), Betanis (JP), Betmiga (EU, RU)
License data	EU EMA: Betmiga US FDA: Mirabegron
Pregnancy category	US: C (Risk not ruled out)
Routes of administration	Oral (tablets)
ATC code	G04BD12 (WHO)
Legal status
Legal status	UK: POM (Prescription only) US: ℞-only ℞ (Prescription only)
Pharmacokinetic data
Bioavailability	29–35%[1]
Protein binding	71%[1]
Metabolism	Hepatic via (direct) glucuronidation, amide hydrolysis, and minimal oxidative metabolism in vivo by CYP2D6 and CYP3A4. Some involvement of butylcholinesterase[1]
Biological half-life	50 hours[1]
Excretion	Urine (55%), faeces (34%)[1]
Identifiers
IUPAC name 2-(2-Amino-1,3-thiazol-4-yl)-N-[4-(2-{[(2R)-2-hydroxy-2-phenylethyl]amino}ethyl)phenyl]acetamide
Synonyms	YM-178
CAS Number	223673-61-8
PubChem (CID)	9865528
ChemSpider	8041219
ECHA InfoCard	100.226.392
Chemical and physical data
Formula	C21H24N4O2S
Molar mass	396.506 g/mol
3D model (Jmol)	Interactive image
SMILES O=C(Nc1ccc(cc1)CCNC[C@H](O)c2ccccc2)Cc3nc(sc3)N
InChI InChI=1S/C21H24N4O2S/c22-21-25-18(14-28-21)12-20(27)24-17-8-6-15(7-9-17)10-11-23-13-19(26)16-4-2-1-3-5-16/h1-9,14,19,23,26H,10-13H2,(H2,22,25)(H,24,27)/t19-/m0/s1 Key:PBAPPPCECJKMCM-IBGZPJMESA-N

Mirabegron (trade name Myrbetriq meer-BET-trick in the US and Betmiga in Europe) is a drug for the treatment of overactive bladder.^[2] It was developed by Astellas Pharma and was approved in the United States in July 2012.^[3]

Mirabegron activates the β₃ adrenergic receptor in the detrusor muscle in the bladder, which leads to muscle relaxation and an increase in bladder capacity.^[4]

Medical uses

Its primary use is in the treatment of overactive bladder.^[1][5][6]

Mirabegron has also recently been shown to activate brown fat and increase metabolism. In a small study of 15 healthy, lean men, Mirabegron was shown to increase basal heart rate, metabolic rate and blood pressure which are signs of cardiovascular stimulation.^[7]

Recently, mirabegron was shown to relax in vitro human and rabbit prostate smooth muscle through activation of β₃ adrenoceptor.^[8] The same group also showed that mirabegron promotes smooth muscle relaxation by α₁ adrenergic receptor blockade.^[9]

Adverse effects

Adverse effects by incidence:^[1][5][6]

Very common (>10% incidence) adverse effects include:

• Elevated blood pressure

Common (1–10% incidence) adverse effects include:

• Dry mouth
• Nasopharyngitis
• Urinary tract infection (UTI)
• Headache
• Influenza
• Constipation
• Dizziness
• Joint pain
• Cystitis
• Back pain
• Upper respiratory tract infection (URTI)
• Sinusitis
• Diarrhea
• High heart rate
• Fatigue
• Abdominal pain
• Neoplasms (cancers)

Rare (<1% incidence) adverse effects include:

• Palpitations
• Blurred vision
• Glaucoma
• Indigestion
• Gastritis
• Abdominal distension
• Rhinitis
• Elevations in liver enzymes (GGTP, AST, ALT and LDH)
• Renal and urinary disorders (e.g., nephrolithiasis, bladder pain)
• Reproductive system disorders (e.g., vulvovaginal pruritus, vaginal infection)
• Skin and subcutaneous tissue disorders (e.g., urticaria, leukocytoclastic vasculitis, rash, pruritus, purpura, lip edema)
• Stevens–Johnson syndrome associated with increased serum ALT, AST and bilirubin
• Urinary retention

References

1. "mirabegron (Rx) - Myrbetriq". Medscape Reference. WebMD. Retrieved 17 November 2013.
2. Gras, J (2012). "Mirabegron for the treatment of overactive bladder". Drugs of today (Barcelona, Spain : 1998). 48 (1): 25–32. doi:10.1358/dot.2012.48.1.1738056. PMID 22384458.
3. Sacco, E; Bientinesi, R; et al. (Apr 2014). "Discovery history and clinical development of mirabegron for the treatment of overactive bladder and urinary incontinence". Expert Opin Drug Discov. 9 (4): 433–48. doi:10.1517/17460441.2014.892923. PMID 24559030.
4. "New Drug Approvals 2012 - Pt. XIV - Mirabegron (MyrbetriqTM)". ChEMBL. 5 July 2012. Retrieved 28 September 2012.
5. "MYRBETRIQ (mirabegron) tablet, film coated, extended release [Astellas Pharma US, Inc.]". DailyMed. Astellas Pharma US, Inc. September 2012. Retrieved 17 November 2013.
6. "Betmiga 25mg & 50mg prolonged-release tablets". electronic Medicines Compendium. Astellas Pharma Ltd. 22 February 2013. Retrieved 17 November 2013.
7. Cypess, Aaron; Weiner, Lauren; Roberts-Toler, Carla; Elía, Elisa; Kessler, Skyler; Kahn, Peter; English, Jeffrey; Chatman, Kelly; Trauger, Sunia; Doria, Alessandro; Kolodny, Gerald (6 January 2015). "Activation of Human Brown Adipose Tissue by a β3-Adrenergic Receptor Agonist". Cell Metabolism. 21 (1): 33–38. doi:10.1016/j.cmet.2014.12.009. PMID 25565203.
8. Calmasini, F. B., T. Z. Candido, E. C. Alexandre, C. A. D'Ancona, D. Silva, M. A. de Oliveira, G. De Nucci, E. Antunes and F. Z. Monica (2015). "The beta-3 adrenoceptor agonist, mirabegron relaxes isolated prostate from human and rabbit: new therapeutic indication?" Prostate 75(4): 440-447.
9. Alexandre, E C; Kiguti, L R; Calmasini, F B; Silva, F H; da Silva, K P; Ferreira, R; Ribeiro, C A; Mónica, F Z; Pupo, A S (2015-10-01). "Mirabegron relaxes urethral smooth muscle by a dual mechanism involving β3-adrenoceptor activation and α1-adrenoceptor blockade". British Journal of Pharmacology: n/a–n/a. doi:10.1111/bph.13367. ISSN 1476-5381.

External links

• Sacco, E.; Bientinesi, R. (2012). "Mirabegron: A review of recent data and its prospects in the management of overactive bladder". Therapeutic Advances in Urology. 4 (6): 315–24. doi:10.1177/1756287212457114. PMC 3491758. PMID 23205058.