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American Journal of Clinical Nutrition, Vol 55, 252S-257S, Copyright © 1992 by The American Society for Clinical Nutrition, Inc

REVIEW ARTICLES

BRL 35135, a potent and selective atypical beta-adrenoceptor agonist

MA Cawthorne, MV Sennitt, JR Arch and SA Smith
Diabetes Programme, SmithKline Beecham Pharmaceuticals, Great Burgh, Epsom, Surrey, UK.

BRL 35135, via its active deesterified metabolite BRL 37344, is a potent example of a new group of beta-adrenoceptor agonists that stimulate selectively a novel beta adrenoceptor that was originally shown to be present in brown adipose tissue in rodents. BRL 35135 produces a dose-related increase in energy expenditure in rodents and, in genetically obese (ob/ob) mice, a dose of 0.5 mg.kg-1.d-1 has significant antiobesity activity. This weight loss is entirely due to loss of fat; muscle protein is preserved. In studies in nonobese men, BRL 35135 (0.1 mg/kg) increased both resting metabolic rate and the thermic response to a glucose load. BRL 35135 is effective in improving glucose tolerance in genetically obese (ob/ob) mice and obese Zucker (fa/fa) rats at doses that have no significant antiobesity activity. The improved glucose tolerance is the result of significant improvement in insulin sensitivity. In 10-d studies in obese and diabetic patients, BRL 35135 produced improvements in glucose tolerance and insulin sensitivity.


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Copyright © 1992 by The American Society for Nutrition