Sawa Masaaki, Harada Hiroshi
Chemistry Research Laboratories, Drug Research Division, Dainippon Sumitomo Pharma Co., Ltd., 33-94 Enoki-cho, Suita, Osaka 564-0053, Japan.
Curr Med Chem. 2006;13(1):25-37.
The beta3-adrenergic receptor (beta3-AR) has been shown to mediate various pharmacological and physiological effects such as lipolysis, thermogenesis, and relaxation of the urinary bladder. Activation of the beta3-AR is thought to be a possible approach for the treatment of obesity, type 2 diabetes mellitus, and frequent urination. Therefore, the beta3-AR is recognized as an attractive target for drug discovery. On the other hand, activation of the beta1- or beta2-AR can cause undesirable side effects such as increased heart rate or muscle tremors. Consequently, a number of recent efforts in this field have been directed toward the design of selective agonists for the beta3-AR. This review summarizes recent advances in beta3-AR agonists with an emphasis on recent attempts to create potent, selective and orally bioavailable small-molecule agonists.
β3肾上腺素能受体（β3-AR）已被证明可介导多种药理和生理效应，如脂肪分解、产热和膀胱舒张。β3-AR的激活被认为是治疗肥胖症、2型糖尿病和尿频的一种可能方法。因此，β3-AR被认为是药物研发的一个有吸引力的靶点。另一方面，β1-或β2-AR的激活会导致不良副作用，如心率加快或肌肉震颤。因此，该领域最近的许多努力都致力于设计β3-AR的选择性激动剂。本综述总结了β3-AR激动剂的最新进展，重点是最近为开发强效、选择性和口服生物可利用的小分子激动剂所做的尝试。
