Sibutramine: a review of the pharmacology of a novel anti-obesity agent.

Sibutramine is a noradrenaline and 5-hydroxytryptamine reuptake inhibitor which causes weight loss in laboratory rodents via effects on both food intake and metabolic rate. Sibutramine's effects are predominantly mediated by two pharmacologically-active metabolites (its primary and secondary amines). Sibutramine and its active metabolites do not cause the release of monoamine neurotransmitters and do not have affinity for their receptors. Sibutramine dose-dependently inhibits 24 h food intake in rats by enhancing the natural physiological process of satiety. Sibutramine also stimulates thermogenesis in rats, producing sustained (> 6 h) increases in oxygen consumption of up to 30%. The thermogenic effect of sibutramine results from central activation of efferent sympathetic activity which, in turn, involves activation of beta 3-adrenoceptors. Sympathetic stimulation of brown adipose tissue via beta 3-adrenoceptors is thought to be the cause of the large, 18 fold increase in brown adipose tissue glucose utilization induced by sibutramine. These dual effects of sibutramine on food intake and thermogenesis explain its anti-obesity effect in animals.