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• W2029380075 abstract "The discovery of a third β-adrenergic receptor (β3-AR) in the early 1980s and the finding that stimulation of this receptor by selective agonists leads to marked weight loss and glycemic improvements in rodent models of obesity and diabetes, respectively, has led to intensive research efforts to develop β3-AR agonists for the treatment of obesity and Type 2 diabetes in humans. Indeed, the ability of β3-AR agonists to simultaneously increase lipolysis, fat oxidation, energy expenditure, and insulin sensitivity suggests that this class of agents may have promising potential as both antiobesity and antidiabetic agents. Unfortunately, several pharmaceutical problems have hampered their development as therapeutic agents in humans over the past 15 years. Major obstacles have been the pharmacological differences between the rodent and human β3-AR, the lack of selectivity of previous compounds for the β3- over β1/β2-ARs, and unsatisfactory pharmacokinetic properties. More recently, clinical studies with a highly (rodent-) selective β3-AR agonist have provided unequivocal evidence that selective β3-AR stimulation can increase lipolysis, fat oxidation, and insulin sensitivity in humans. Meanwhile, cloning of the human β3-AR has allowed the development of novel compounds that are specifically targeted at the human receptor. This new generation of compounds has shown promising results in nonhuman primates and in Phase 1 studies in humans. Once human β3-AR selective compounds with satisfactory pharmacokinetic properties become available, clinical testing will reveal whether their effects are sufficient and safe in the long term to allow the use of these agonists for the treatment of obesity and diabetes in humans. Drug Dev. Res. 51:80–93, 2000. © 2000 Wiley-Liss, Inc." @default.
• W2029380075 created "2016-06-24" @default.
• W2029380075 creator A5066361209 @default.
• W2029380075 creator A5069796351 @default.
• W2029380075 date "2000-01-01" @default.
• W2029380075 modified "2023-09-24" @default.
• W2029380075 title "Development of ?3-adrenoceptor agonists as antiobesity and antidiabetes drugs in humans: Current status and future prospects" @default.
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• W2029380075 doi "https://doi.org/10.1002/1098-2299(200010)51:2<80::aid-ddr4>3.0.co;2-e" @default.
• W2029380075 hasPublicationYear "2000" @default.

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