BRL 35135, a potent and selective atypical beta-adrenoceptor agonist.
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.
Cawthorne
M A
MA
Diabetes Programme, SmithKline Beecham Pharmaceuticals, Great Burgh, Epsom, Surrey, UK.
Sennitt
M V
MV
Arch
J R
JR
Smith
S A
SA
D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D006801:Humans; D009765:Obesity / Q000188:drug therapy*; D010627:Phenethylamines / Q000494:pharmacology* / Q000627:therapeutic use
D000318:Adrenergic beta-Agonists; D010627:Phenethylamines; C063157:BRL 35135