Jon Arch talk on β3-adrenoceptor agonists for Hans Zaagsma symposium published as review

24 July 2008

Jon Arch, Deputy Director of Metabolic Research, Clore Laboratory, University of Buckingham, UK, discusses lessons learned from the discovery of β-adrenoceptors and their agonists in a recently published review in Naunyn-Schmiedeberg’s Archives of Pharmacology. The review was an invited talk at the symposium held in honour of Professor Hans Zaagsma on the occasion of his retirement.

The review covers three areas.

First, β3-adrenoceptor agonists selectively stimulate fat oxidation and this is probably why they improve insulin sensitivity and reduce body fat whilst preserving lean body mass. Other stimulants of fat oxidation are likely to have similar effects on insulin sensitivity and body composition and are potentially useful for the treatment of type 2 diabetes and obesity, whatever their molecular target.

Second, β3-adrenoceptor agonists cause marked acute increases in energy expenditure, whereas stimulants of fat oxidation that do not act on β-adrenoceptors cause more sustained and less easily detectable increases. This feature indicates whether hormones, such as leptin, or drugs, such as sibutramine, stimulate fat oxidation by increasing sympathetic activity.

Third, studies on β3-adrenoceptors have shown how the pharmacology of a receptor can vary according to where or how the receptor is expressed, or what response is measured.

The full reference is:

Jonathan R. S. Arch   The discovery of drugs for obesity, the metabolic effects of leptin and variable receptor pharmacology: perspectives from β3-adrenoceptor agonists. Nunyn-Schmiedeberg’s Archives of Pharmacology 2008 Aug;378(2):225–240. Epub 9 July 2008. doi:10.1007/s00210-008-0271-1