Sibutramine (trade name Meridia in the USA, Reductil in Europe and other countries), usually as sibutramide hydrochloride monohydrate, is an orally administered agent for the treatment of obesity. It is a centrally acting stimulant chemically related to amphetamines. Sibutramine is classified as a Schedule IV controlled substance in the United States. In October 2010, Sibutramine was withdrawn from Canadian and U.S. markets due to concerns that the drug increases the risk of heart attack and stroke in patients with a history of heart disease.
Sibutramine produces its therapeutic effects by inhibition of norepinephrine (NE), serotonin (5-hydroxytryptamine, 5-HT), and to a lesser extent, dopamine reuptake at the neuronal synapse. By inhibiting the reuptake of these neurotransmitters, sibutramine promotes a sense of satiety and decrease in appetite, thereby reducing food intake. Data from animal studies also suggest that sibutramine may also increase energy expenditure through thermogenic effects in both the basal and fed states, but this has not been confirmed in humans. Sibutramine and its major pharmacologically active metabolites (M1 and M2) do not act via release of monoamines.
Sibutramine is metabolized in the liver principally by the cytochrome P450 (3A4) isoenzyme, to desmethyl metabolites, M1 and M2. These active metabolites are further metabolized by hydroxylation and conjugation to pharmacologically inactive metabolites, M5 and M6. Approximately 85% (range 68-95%) of a single orally administered radiolabeled dose was excreted in urine and feces over a 15-day collection period with the majority of the dose (77%) excreted in the urine. The primary route of excretion for M1 and M2 is hepatic metabolism and for M5 and M6 is renal excretion.
(R)-warfarin Sibutramine may increase the antiplatelet activities of (R)-warfarin.
(S)-Warfarin Sibutramine may increase the antiplatelet activities of (S)-Warfarin.
2,5-Dimethoxy-4-ethylthioamphetamine The risk or severity of adverse effects can be increased when 2,5-Dimethoxy-4-ethylthioamphetamine is combined with Sibutramine.
3,5-diiodothyropropionic acid The therapeutic efficacy of 3,5-diiodothyropropionic acid can be decreased when used in combination with Sibutramine.
4-Bromo-2,5-dimethoxyamphetamine The risk or severity of adverse effects can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Sibutramine.
4-hydroxycoumarin The metabolism of 4-hydroxycoumarin can be decreased when combined with Sibutramine.
4-Methoxyamphetamine The risk or severity of adverse effects can be increased when 4-Methoxyamphetamine is combined with Sibutramine.
5-androstenedione The metabolism of 5-androstenedione can be decreased when combined with Sibutramine.
5-methoxy-N,N-dimethyltryptamine The risk or severity of adverse effects can be increased when 5-methoxy-N,N-dimethyltryptamine is combined with Sibutramine.
6-Deoxyerythronolide B The metabolism of Sibutramine can be decreased when combined with 6-Deoxyerythronolide B.
Chris Senanayake, "Methods of preparing didesmethylsibutramine and other sibutramine derivatives." U.S. Patent US20020183554, issued December 05, 2002.