Acute effect of L-796568, a novel beta 3-adrenergic receptor agonist, on energy expenditure in obese men.
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.
van Baak
Marleen A
MA
Nutrition and Toxicology Research Institute (NUTRIM), Department of Human Biology, Maastricht University, The Netherlands. m.vanbaak@hb.unimaas.nl
Hul
Gabby B J
GB
Toubro
Søren
S
Astrup
Arne
A
Gottesdiener
Keith M
KM
DeSmet
Marina
M
Saris
Wim H M
WH
D000284:Administration, Oral; D000293:Adolescent; D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000097:blood / Q000494:pharmacology*; D000328:Adult; D000704:Analysis of Variance; D019440:Anti-Obesity Agents / Q000008:administration & dosage* / Q000097:blood; D018592:Cross-Over Studies; D004734:Energy Metabolism / Q000187:drug effects*; D006801:Humans; D008066:Lipolysis / Q000187:drug effects / Q000502:physiology; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism*; D013449:Sulfonamides / Q000008:administration & dosage* / Q000097:blood; D013844:Thiazoles / Q000008:administration & dosage* / Q000097:blood; D000096926:Benzenesulfonamides
D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists; D019440:Anti-Obesity Agents; D013449:Sulfonamides; D013844:Thiazoles; C415563:N-(4-(2-((2-hydroxy-2-(3-pyridinyl)ethyl)amino)ethyl)phenyl)-4-(4-(4-(trifluoromethyl)phenyl)thiazol-2-yl)benzenesulfonamide; D000096926:Benzenesulfonamides