Thermogenic effects of various beta-adrenoceptor agonists in humans: their potential usefulness in the treatment of obesity.
The thermogenic effect of various beta-agonists was studied in humans by using indirect calorimetry. Epinephrine was found to be markedly thermogenic: at infusion rates of 0.01, 0.03, and 0.1 microgram.min-1.kg fat-free mass-1 resting energy expenditure (REE) increased by 8%, 16%, and 29%, respectively; in addition, a dose-dependent increase in heart rate was observed. Dopamine at high infusion rates also induces beta-agonist effects: at 5 and 10 micrograms.min-1.kg-1, REE increased by 6% and 15%, respectively, an effect that could be mediated by the release of endogenous norepinephrine. The phenethanolamine derivative Ro 16-8714 given per os at a single dose of 5 and 20 mg led to an increase of REE of 10% and 21%, whereas heart rate was enhanced by 8% and 49%, respectively. The new beta-adrenoreceptor agonist Ro 40-2148, given per os to six normal-weight young subjects at a single dose of 200 or 400 mg, induced no significant change in REE, whereas after 800 mg, REE was increased in all subjects (+3 to +17%, mean + 8%) without inducing tachycardia.
Jéquier
E
E
Institute of Physiology, University of Lausanne, Switzerland.
Munger
R
R
Felber
J P
JP
D000318:Adrenergic beta-Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D001833:Body Temperature Regulation / Q000187:drug effects*; D004298:Dopamine / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D009638:Norepinephrine / Q000494:pharmacology; D009765:Obesity / Q000188:drug therapy*
D000318:Adrenergic beta-Agonists; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine