Screening of drugs for thermogenic anti-obesity properties: antidepressants.

Twelve antidepressant drugs, currently in clinical use, were screened for thermogenic properties on the basis of their ability to stimulate the activity of the sympathetic nervous system via an inhibitory effect on noradrenaline reuptake into the sympathetic neurons. Drug screening was carried out on mice made obese by hypothalamic lesioning using monosodium glutamate. Preliminary experiments, based on changes in body weight and food intake in response to increased doses of the drugs, indicate that most of the twelve antidepressants possess thermogenic potential. In particular, butriptyline, protriptyline and nortriptyline were most effective in causing marked losses in body weight without altering the food intake of the mice. The potent anti-obesity thermogenic properties of these three antidepressants were confirmed during a 10-week energy balance study involving measurements of energy expenditure over the entire period by the comparative carcass method, as well as by measurement of 24 h oxygen consumption. These studies indicate that the methodology employed in the preliminary screening is valid for identifying drugs with thermogenic potential, and demonstrate that many antidepressants currently in clinical use have marked thermogenic properties, and could therefore influence the nutritional status of patients under drug therapy.