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• W2006081805 abstract "Historical setting In the latter part of the 1970s and the early 1980s three pharmaceutical companies were attempting to design drugs that would retain the thermogenic and antiobesity activity in rodents of nonselective sympathomimetic agents, while lacking the undesirable effects elicited by such agents, in particular increased heart rate and tremor. These companies were Lilly [Yen et al. 1984] Beecham Pharmaceuticals (for which this author worked) [Arch et al. 1984b], and Hoffman-La-Roche [Meier et al. 1984]. Others revealed their interest a little later [Holloway et al. 1991]. From this work, Beecham Pharmaceuticals identified compounds that activated an ‘atypical’ b-adrenoceptor in rodent brown and white adipocytes [Arch et al. 1984a]. From 1974 Zaagsma and colleagues had gathered evidence that the rat white adipocyte b-adrenoceptor was atypical but they had used only antagonists [Harms et al. 1974]. Antagonists mostly display low potency at the atypical b-adrenoceptor compared with b1and b2-adrenoceptors. Even before Zaagsma’s work, Furchgott had reviewed antagonist data that showed that the b-adrenoceptor in various parts of the gut is atypical [Furchgott, 1972]. Tan and Curtis-Prior suggested in 1983 that the adipocyte receptor should be called the b3-adrenoceptor, but it was not until 1989 that I argued strongly for the use of this name to describe the atypical adipocyte b-adrenoceptor [Arch, 1989]. Soon afterwards, the human b3-adrenoceptor was cloned [Emorine et al. 1989] and subsequent work showed that the rodent b3-adrenoceptor is identical to the atypical b-adrenoceptor found in both adipocytes and the gut. It also became clear that the b3-adrenoceptor is primarily responsible for thermogenesis (increased energy expenditure) and fat loss in response to sympathetic stimulation in obese rodents. Fuller versions of this sequence of events have been published previously [Arch, 2008; Arch and Kaumann, 1993]." @default.
• W2006081805 created "2016-06-24" @default.
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• W2006081805 date "2011-02-18" @default.
• W2006081805 modified "2023-10-12" @default.
• W2006081805 title "Challenges in β₃-adrenoceptor agonist drug development" @default.
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• W2006081805 doi "https://doi.org/10.1177/2042018811398517" @default.
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