Acute effect of L-796568, a novel beta 3-adrenergic receptor agonist, on energy expenditure in obese men

Clin Pharmacol Ther. 2002 Apr;71(4):272-9. doi: 10.1067/mcp.2002.122527.


Objective: Our objective was to investigate the thermogenic efficacy of single oral doses of the novel beta(3)-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] in humans.

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, or leptin were found.

Conclusions: Single-dose administration of 1000 mg of the novel beta(3)-adrenergic receptor agonist L-796568 increased lipolysis and energy expenditure in overweight men. This is the first study to show such an effect of beta(3)-adrenergic receptor agonists in humans without significant evidence for beta(2)-adrenergic receptor involvement.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adrenergic beta-3 Receptor Agonists*
  • Adrenergic beta-Agonists / blood
  • Adrenergic beta-Agonists / pharmacology*
  • Adult
  • Analysis of Variance
  • Anti-Obesity Agents / administration & dosage*
  • Anti-Obesity Agents / blood
  • Cross-Over Studies
  • Energy Metabolism / drug effects*
  • Humans
  • Lipolysis / drug effects
  • Lipolysis / physiology
  • Middle Aged
  • Obesity / drug therapy
  • Obesity / metabolism*
  • Sulfonamides / administration & dosage*
  • Sulfonamides / blood
  • Thiazoles / administration & dosage*
  • Thiazoles / blood


  • Adrenergic beta-3 Receptor Agonists
  • Adrenergic beta-Agonists
  • Anti-Obesity Agents
  • N-(4-(2-((2-hydroxy-2-(3-pyridinyl)ethyl)amino)ethyl)phenyl)-4-(4-(4-(trifluoromethyl)phenyl)thiazol-2-yl)benzenesulfonamide
  • Sulfonamides
  • Thiazoles