Acute effect of L‐796568, a novel β3‐adrenergic receptor agonist, on energy expenditure in obese men
MA van Baak, GBJ Hul, S Toubro… - Clinical …, 2002 - Wiley Online Library
Clinical Pharmacology & Therapeutics, 2002•Wiley Online Library
Objective Our objective was to investigate the thermogenic efficacy of single oral doses of
the novel β3‐adrenergic receptor agonist L‐796568 [(R)‐N‐[4‐[2‐[[2‐hydroxy‐2‐(3‐
pyridinyl) ethyl] amino] ethyl]‐phenyl]‐4‐[4‐[4‐(trifluoromethyl) phenyl] thiazol‐2‐yl]‐
benzenesulfonamide, dihydrochloride] inhumans. Methods Twelve healthy overweight to
obese men participated in this 2‐center, 3‐period, randomized, placebo‐controlled,
crossover trial. In each period subjects received 250 mg L‐796568, 1000 mg L‐796568, or …
the novel β3‐adrenergic receptor agonist L‐796568 [(R)‐N‐[4‐[2‐[[2‐hydroxy‐2‐(3‐
pyridinyl) ethyl] amino] ethyl]‐phenyl]‐4‐[4‐[4‐(trifluoromethyl) phenyl] thiazol‐2‐yl]‐
benzenesulfonamide, dihydrochloride] inhumans. Methods Twelve healthy overweight to
obese men participated in this 2‐center, 3‐period, randomized, placebo‐controlled,
crossover trial. In each period subjects received 250 mg L‐796568, 1000 mg L‐796568, or …
Objective
Our objective was to investigate the thermogenic efficacy of single oral doses of the novel β3‐adrenergic receptor agonist L‐796568 [(R)‐N‐[4‐[2‐[[2‐hydroxy‐2‐(3‐pyridinyl)ethyl]amino]ethyl]‐phenyl]‐4‐[4‐[4‐(trifluoromethyl)phenyl]thiazol‐2‐yl]‐benzenesulfonamide, dihydrochloride] inhumans.
Methods
Twelve healthy overweight to obese men participated in this 2‐center, 3‐period, randomized, placebo‐controlled, crossover trial. In each period subjects received 250 mg L‐796568, 1000 mg L‐796568, or placebo. Energy expenditure and respiratory quotient were determined by indirect calorimetry; blood samples were taken; and ear temperature, heart rate, and blood pressure were measured at baseline and during the 4‐hour period after administration.
Results
Energy expenditure increased significantly after the 1000‐mg dose (about 8%) and this was accompanied by an increase in plasma glycerol and free fatty acid concentrations. Systolic blood pressure also increased significantly. No changes in heart rate, diastolic blood pressure, ear temperature, plasma catecholamine, potassium, orleptin were found.
Conclusions
Single‐dose administration of 1000 mg of the novel β3‐adrenergic receptor agonist L‐796568 increased lipolysis and energy expenditure in overweight men. This is the first study to show such an effect of β3‐adrenergic receptor agonists in humans without significant evidence for β2‐adrenergic receptor involvement.
Clinical Pharmacology & Therapeutics (2002) 71, 272–279; doi: 10.1067/mcp.2002.122527
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