Sibutramine

Sibutramine is a a centrally-acting serotonin-norepinephrine reuptake inhibitor structurally related to amphetamines. Originally used in the treatment of depression, it is now used to help obese and overweight patients lose weight, and along with Orlistat, in 2008 was the only drug licensed for use in the UK. It has been associated with increased cardiovascular events and stroke, and has since been withdrawn from the market.

Sibutramine acts within the hypothalamus by preventing reuptake of both noradrenaline and serotonin. This inhibition causes the patient increased feelings of satiety, a decreased appetite, and a corresponding reduced intake of food which results in weight loss. Some studies have shown that sibutramine may increase thermogenesis and as such, contribute to weight loss, but there have also been other studies in which no such effects were shown, and it seems that this action contributes in, at most a minor way to weight loss. It is also thought that sibutramine may effect levels of the hormones leptin and ghrelin, as well as central neuropeptide Y (NPY), and proopiomelanocortin (POMC) mRNA. Sibutramine treatment differs to orlistat in relation to leptin, as, when using sibutramine, transfer of leptin into the brain is maintained or even increased during weight loss which does not happen when using orlistat.

Sibutramine was first marketed by Knoll Pharmaceuticals and subsequently by Abbott Laboratories under various brand names including Reductil, Meridia and Sibutrex. It is classified as a Schedule IV controlled substance in the U.S.A.