MK-4618

Vibegron (MK-4618) is a potent, highly selective β3-adrenoceptor agonist (EC50=1.1 nM). Vibegron can be used for severe urgency urinary incontinence related to overactive bladder[1][2][3].

Research Areas >> Others

Signaling Pathways >> GPCR/G Protein >> Adrenergic Receptor

β3 adrenoceptor:1.1 nM (EC50)

Vibegron (1~12 μΜ; i.v.) exhibits dose dependent decreases in micturition pressure and increases in functional bladder capacity[3]. Vibegron (30 mg/kg; p.o.; 4 weeks) upregulates mRNA levels of type 1, type 3 collagen, TGF‐β1, and HIF‐1α[4]. Vibegron (1 and 10 mg/kg; i.v.; interval 30 minutes) (10 mg/kg) in oxo-M-treated rats makes bladder capacity significantly decreased compared with oxo-M-not treated rats (intravesical instillation of vehicle)[5]. Animal Model: Rat Dosage: 1~12 μΜ Administration: I.v. Result: Exhibited dose dependent decreases in micturition pressure and increases in functional bladder capacity. Animal Model: Female C57BL/6N mice (9 weeks old) Dosage: 30 mg/kg Administration: P.o.; 4 weeks Result: Upregulated mRNA levels of type 1, type 3 collagen, TGF‐β1, and HIF‐1α at 4 weeks. Animal Model: Female F344 rats (120–160 g) Dosage: 1 and 10 mg/kg Administration: I.v.; Interval 30 minutes Result: Vibegron (10 mg/kg) in oxo-M-treated rats made bladder capacity significantly decreased compared with oxo-M-not treated rats (intravesical instillation of vehicle).

[1]. Yoshida M, et al. Efficacy of vibegron, a novel β3-adrenoreceptor agonist, on severe urgency urinary incontinence related to overactive bladder: post hoc analysis of a randomized, placebo-controlled, double-blind, comparative phase 3 study. BJU Int. 2020;125(5):709-717.

[2]. Yoshida M, et al. Efficacy of novel β3 -adrenoreceptor agonist vibegron on nocturia in patients with overactive bladder: A post-hoc analysis of a randomized, double-blind, placebo-controlled phase 3 study. Int J Urol. 2019;26(3):369-375.

[3]. Edmondson SD, et al. Discovery of Vibegron: A Potent and Selective β3 Adrenergic Receptor Agonist for the Treatment of Overactive Bladder. J Med Chem. 2016;59(2):609-623.

[4]. Gotoh D, et al. Effects of a new β3-adrenoceptor agonist, vibegron, on neurogenic bladder dysfunction and remodeling in mice with spinal cord injury. Neurourol Urodyn. 2020;39(8):2120-2127.

[5]. Furuta A, et al. Additive effects of intravenous and intravesical application of vibegron, a β3-adrenoceptor agonist, on bladder function in rats with bladder overactivity. Naunyn Schmiedebergs Arch Pharmacol. 2020;393(11):2073-2080.