ABSTRACT During the past 15 years research interests in obesity pharmacotherapy have focused upon sympathomimetic stimulation of thermogenesis. This approach follows several lines of evidence pointing to an important role of the sympathetic nervous system (SNS), via its heat-producing neurotransmitter noradrenaline (NA), in energy balance regulation, and that a reduction in its functional state contribute to the diminished thermogenesis leading to obesity. Drugs that mimic the activity of the SNS and increase the metabolic rate therefore offer considerable therapeutic potential, and provide a rational pharmacological approach for obesity treatment. This has led to the testing of a wide variety of sympathetic stimulants already in clinical use for other treatment, as well as some β-agonists used experimentally for the production of leaner livestock. In addition, several pharmaceutical companies, largely motivated by evidence suggesting that the adrenergic control of thermogenesis involves mechanisms other than conventional α and β adrenoceptors, have been successful in putting forward a new generation of atypical β-agonists (often termed β3 agonists). This paper reviews briefly the role of the SNS in obesity, and then analyses the applicability and effectiveness of various strategies of sympathomimetic drug activation of thermogenesis in the management of obesity.
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