生物活性

• 靶点	Adrenergic Receptor β3 EC50:22.4nM

• 描述β₃-AR is a G protein-coupled receptor. Functional β₃-AR-mediated responses have been observed in human brown and white fat cells, where they mediate lipolysis; and in gall bladder, stomach, small intestine, prostate, colon, and bladder, where they evoke relaxation. Mirabegron is a selective β₃-adrenoceptor agonist. Mirabegron concentration-dependently increased the accumulation of cAMP in CHO cells expressing human β₃-ARs, with an EC₅₀ value and I.A. of 22.4 nM and 0.8, respectively. Mirabegron concentration-dependently relaxed rat bladder smooth muscle strips precontracted with 10^-6 M CCh with EC₅₀ value of 5.1 μM. The maximal relaxant effect of mirabegron was 94.0±1.0%, that of CCh, indicating that mirabegron acts a full agonist in the rat bladder. Mirabegron concentration-dependently relaxed human bladder smooth muscle strips precontracted with 10^-7 M CCh with EC₅₀ value of 0.78 μM. The maximal relaxant effect of mirabegron was 89.4±2.3%. Mirabegron produced a dose-dependent decrease in the frequency of rhythmic bladder contraction in anesthetized rats^[3]. SAAs (single-unit afferent activities) of both Aδ-fibers and C-fibers in response to bladder filling significantly decreased after mirabegron administration in a dose-dependent manner (Nerves with conduction velocities (CVs) >2.5 m/s were designated as Aδ-fibers, and nerves with CVs<2.5 m/s were designated as C-fibers)^[4].
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT00337090	Overactive Bladder	Phase 2	Completed	-	-
  NCT02811289	Type 2 Diabetes	Not Applicable	Completed	-	Canada, Quebec ... more >> centre de recherche du CHUS Sherbrooke, Quebec, Canada, J1H 5N4 Collapse <<
  NCT01043666	Urinary Bladder, Overactive	Phase 3	Completed	-	China ... more >> Beijing, China Dalian, China Fuzhou, China Guangzhou, China Hangzhou, China Hubei, China Hunan, China Jiangsu, China Liaoning, China Nanjing, China Shanghai, China India Ahmedabad, India Gurgaon, India Jaipur, India Lucknow, India New Delhi, India Pune, India Korea, Republic of Busan, Korea, Republic of Chungcheong Namdo, Korea, Republic of Daegu, Korea, Republic of Daejeon, Korea, Republic of Gwangju, Korea, Republic of Gyeonggi, Korea, Republic of Incheon, Korea, Republic of Jeollabuk, Korea, Republic of Jeollanam, Korea, Republic of Kyonggi, Korea, Republic of Seoul, Korea, Republic of Taiwan Chia-Yi, Taiwan Hualien, Taiwan Kaohsiung, Taiwan Taichung, Taiwan Tainan, Taiwan Taipei, Taiwan Taoyuan, Taiwan Collapse <<

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• 参考文献

• [1] Takusagawa S, Miyashita A, et al. In vitro inhibition and induction of human cytochrome P450 enzymes by mirabegron, a potent and selective β3-adrenoceptor agonist. Xenobiotica. 2012 Dec;42(12):1187-96.

  [2] Takasu T, Ukai M, et al. Effect of (R)-2-(2-aminothiazol-4-yl)-4'-{2-[(2-hydroxy-2-phenylethyl)amino] ethyl} acetanilide (YM178), a novel selective beta3-adrenoceptor agonist, on bladder function. J Pharmacol Exp Ther. 2007 May;321(2):642-7.

  [3] Takasu T, Ukai M, Sato S, et al. Effect of (R)-2-(2-aminothiazol-4-yl)-4'-{2-[(2-hydroxy-2-phenylethyl)amino]ethyl} acetanilide (YM178), a novel selective beta3-adrenoceptor agonist, on bladder function. J Pharmacol Exp Ther. 2007;321(2):642‐647

  [4] Aizawa N, Homma Y, Igawa Y. Effects of mirabegron, a novel β3-adrenoceptor agonist, on primary bladder afferent activity and bladder microcontractions in rats compared with the effects of oxybutynin. Eur Urol. 2012;62(6):1165‐1173