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 2 3 4 5 6 7 "mirabegron (Rx) - Myrbetriq". Medscape Reference. WebMD. Retrieved 17 November 2013.
↑ 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.
↑ 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.
↑ "New Drug Approvals 2012 - Pt. XIV - Mirabegron (MyrbetriqTM)". ChEMBL. 5 July 2012. Retrieved 28 September 2012.
1 2 "MYRBETRIQ (mirabegron) tablet, film coated, extended release [Astellas Pharma US, Inc.]". DailyMed. Astellas Pharma US, Inc. September 2012. Retrieved 17 November 2013.
1 2 "Betmiga 25mg & 50mg prolonged-release tablets". electronic Medicines Compendium. Astellas Pharma Ltd. 22 February 2013. Retrieved 17 November 2013.
↑ 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.
↑ 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.
↑ 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.

Urologicals, including antispasmodics (G04B)

Acidifiers	Ammonium chloride Calcium chloride

Urinary antispasmodics (primarily antimuscarinics)	Darifenacin Emepronium Fesoterodine Flavoxate Imidafenacin Meladrazine Mirabegron Oxybutynin Propiverine Solifenacin Terodiline Tolterodine Trospium chloride

Other urologicals	Urea analogues: Acetohydroxamic acid Salicylhydroxamic acid Other: Collagen Dimethyl sulfoxide Magnesium hydroxide Pentosan polysulfate Phenazopyridine Phenyl salicylate Succinimide

Adrenergic receptor modulators

α₁

Agonists 6-FNE Amidephrine Anisodine Buspirone Cirazoline Corbadrine Dexisometheptene Dipivefrine Dopamine Droxidopa (L-DOPS) Ephedrine Epinephrine Etilefrine Etilevodopa Ethylnorepinephrine Indanidine Isometheptene L-DOPA (levodopa) L-Phenylalanine L-Tyrosine Melevodopa Metaraminol Methoxamine Methyldopa Midodrine Naphazoline Norepinephrine Octopamine (drug) Oxymetazoline Phenylephrine Phenylpropanolamine Pseudoephedrine Synephrine Tetryzoline Tiamenidine XP21279 Xylometazoline

Antagonists Abanoquil Adimolol Ajmalicine Alfuzosin Amosulalol Anisodamine Arotinolol Atiprosin Atypical antipsychotics (e.g., clozapine, olanzapine, quetiapine, risperidone) Benoxathian Buflomedil Bunazosin Carvedilol Corynanthine Dapiprazole Domesticine Doxazosin Ergolines (e.g., ergotamine, dihydroergotamine, lisuride, terguride) Etoperidone Eugenodilol Fenspiride Hydroxyzine Indoramin Ketanserin L-765,314 Labetalol mCPP Mepiprazole Metazosin Monatepil Moxisylyte Naftopidil Nantenine Nefazodone Neldazosin Niaprazine Nicergoline Niguldipine Pardoprunox Pelanserin Phendioxan Phenoxybenzamine Phentolamine Piperoxan Prazosin Quinazosin Ritanserin Silodosin Spiperone Talipexole Tamsulosin Terazosin Tiodazosin Tolazoline Trazodone Tetracyclic antidepressants (e.g., amoxapine, maprotiline, mianserin) Tricyclic antidepressants (e.g., amitriptyline, clomipramine, doxepin, imipramine, trimipramine) Trimazosin Typical antipsychotics (e.g., chlorpromazine, fluphenazine, loxapine, thioridazine) Urapidil WB-4101 Zolertine

α₂

Agonists (R)-3-Nitrobiphenyline 4-NEMD 6-FNE Amitraz Apraclonidine Brimonidine Cannabivarin Clonidine Corbadrine Detomidine Dexmedetomidine Dihydroergotamine Dipivefrine Dopamine Droxidopa (L-DOPS) Etilevodopa Ephedrine Ergotamine Epinephrine Etilefrine Ethylnorepinephrine Guanabenz Guanfacine Guanoxabenz L-DOPA (levodopa) L-Phenylalanine L-Tyrosine Lofexidine Medetomidine Melevodopa Methyldopa Mivazerol Naphazoline Norepinephrine Oxymetazoline Phenylpropanolamine Piperoxan Pseudoephedrine Rilmenidine Romifidine Talipexole Tetrahydrozoline Tiamenidine Tizanidine Tolonidine Urapidil XP21279 Xylazine Xylometazoline

Antagonists 1-PP Adimolol Aptazapine Atipamezole Atypical antipsychotics (e.g., asenapine, clozapine, lurasidone, paliperidone, quetiapine, risperidone, zotepine) Azapirones (e.g., buspirone, tandospirone) BRL-44408 Buflomedil Cirazoline Efaroxan Esmirtazapine Fenmetozole Fluparoxan Idazoxan mCPP Mianserin Mirtazapine NAN-190 Olanzapine Pardoprunox Phentolamine Phenoxybenzamine Piperoxan Piribedil Rauwolscine Rotigotine SB-269970 Setiptiline Spiroxatrine Sunepitron Tolazoline Typical antipsychotics (e.g., chlorpromazine, fluphenazine, loxapine, thioridazine) Yohimbine

Agonists Abediterol Alifedrine Amibegron Arbutamine Arformoterol Arotinolol BAAM Bambuterol Befunolol Bitolterol Broxaterol Buphenine Carbuterol Carmoterol Cimaterol Clenbuterol Corbadrine Denopamine Dipivefrine Dobutamine Dopamine Dopexamine Droxidopa (L-DOPS) Ephedrine Epinephrine Etafedrine Etilefrine Etilevodopa Ethylnorepinephrine Fenoterol Formoterol Hexoprenaline Higenamine Indacaterol Isoetarine Isoprenaline Isoxsuprine L-DOPA (levodopa) L-Phenylalanine L-Tyrosine Levosalbutamol Mabuterol Melevodopa Methoxyphenamine Methyldopa Mirabegron Norepinephrine Orciprenaline Oxyfedrine PF-610355 Phenylpropanolamine Pirbuterol Prenalterol Ractopamine Procaterol Pseudoephedrine Reproterol Rimiterol Ritodrine Salbutamol Salmeterol Solabegron Terbutaline Tretoquinol Tulobuterol Vilanterol Xamoterol XP21279 Zilpaterol Zinterol

Antagonists Acebutolol Adaprolol Adimolol Afurolol Alprenolol Alprenoxime Amosulalol Ancarolol Arnolol Arotinolol Atenolol Befunolol Betaxolol Bevantolol Bisoprolol Bopindolol Bornaprolol Brefonalol Bucindolol Bucumolol Bufetolol Bufuralol Bunitrolol Bunolol Bupranolol Butaxamine Butidrine Butofilolol Capsinolol Carazolol Carpindolol Carteolol Carvedilol Celiprolol Cetamolol Cicloprolol Cinamolol Cloranolol Cyanopindolol Dalbraminol Dexpropranolol Diacetolol Dichloroisoprenaline Dihydroalprenolol Dilevalol Diprafenone Draquinolol Ecastolol Epanolol Ericolol Ersentilide Esatenolol Esprolol Eugenodilol Exaprolol Falintolol Flestolol Flusoxolol Hydroxycarteolol Hydroxytertatolol ICI-118,551 Idropranolol Indenolol Indopanolol Iodocyanopindolol Iprocrolol Isoxaprolol Isamoltane Labetalol Landiolol Levobetaxolol Levobunolol Levomoprolol Medroxalol Mepindolol Metipranolol Metoprolol Moprolol Nadolol Nadoxolol Nebivolol Nifenalol Nipradilol Oxprenolol Pacrinolol Pafenolol Pamatolol Pargolol Penbutolol Pindolol Practolol Primidolol Procinolol Pronethalol Propafenone Propranolol Ridazolol Ronactolol Soquinolol Sotalol Spirendolol SR 59230A Sulfinalol Talinolol Tazolol Tertatolol Tienoxolol Tilisolol Timolol Tiprenolol Tolamolol Toliprolol Xibenolol Xipranolol

See also: Dopaminergics

Melatonergics

Serotonergics

Monoamine reuptake and release modulators

Monoamine metabolism modulators

Monoamine neurotoxins

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