Thermogenic drugs as a strategy for treatment of obesity.
There is accumulating evidence to support the hypothesis that a low-energy-output phenotype is at high risk of weight gain and obesity, irrespective of whether this is owing to a low resting metabolic rate and/or physical inactivity. The low-energy-output phenotype is associated with impaired appetite control, which is improved if energy output is increased. This is the background for pharmacologic stimulation of energy expenditure as a tool to improve the results of obesity management. Targets are the leptin receptors, the sympathetic nervous system and its peripheral beta-adrenoceptors, selective thyroid hormone derivatives, and stimulation of the mitochondrial uncoupling proteins. Currently available compounds such as recombinant leptin, ephedrine/caffeine, and sibutramine possess thermogenic properties owing to their activation of the sympathoadrenal system. Compounds acting selectively on the human beta3-adrenoceptor are still promising tools to achieve a sustained stimulation of lipolysis and energy expenditure, and several are in the pipeline.
Astrup
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Research Department of Human Nutrition, RVA University, Copenhagen, Denmark. ast@kvl.dk
D000311:Adrenal Glands / Q000187:drug effects / Q000502:physiology; D019440:Anti-Obesity Agents / Q000627:therapeutic use*; D002110:Caffeine / Q000008:administration & dosage / Q000627:therapeutic use; D003503:Cyclobutanes / Q000627:therapeutic use; D004734:Energy Metabolism / Q000187:drug effects; D004809:Ephedrine / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D020738:Leptin / Q000627:therapeutic use; D009765:Obesity / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000627:therapeutic use; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D022722:Thermogenesis / Q000187:drug effects
D019440:Anti-Obesity Agents; D003503:Cyclobutanes; D020738:Leptin; D011994:Recombinant Proteins; D002110:Caffeine; D004809:Ephedrine; C058254:sibutramine