Top Gene Interactions
- Metabolism: Hepatic Route of Elimination: 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. Half Life: 1.1 hours
- Uses/Sources: For the treatment of obesity.
- Health Effects: Using large amounts of these drugs can result in a condition known as amphetamine psychosis -- which can result in auditory, visual and tactile hallucinations, intense paranoia, irrational thoughts and beliefs, delusions, and mental confusion.
- Symptoms: Side effects include dry mouth, anorexia, insomnia, constipation and headache.
- Treatment: Treatment should consist of general measures employed in the management of overdosage: an airway should be established as needed; cardiac and vital sign monitoring is recommended; general symptomatic and supportive measures should be instituted. Cautious use of p-blockers may be indicated to control elevated blood pressure or tachycardia. (L1712)
- Route of Exposure: Rapid absorption following oral administration. Absolute bioavailability is not known, but at least 77% of a single oral dose of sibutramine is absorbed.
Mechanism of Action
|Target Name||Mechanism of Action||References|
5-hydroxytryptamine receptor 2A
5-hydroxytryptamine receptor 2C
5-hydroxytryptamine receptor 2B
Sodium-dependent dopamine transporter
Sodium-dependent serotonin transporter
Sodium-dependent noradrenaline transporter
|Sibutramine produces its therapeutic effects by norepinephrine (NE), serotonin reuptake (5-hydroxytryptamine, 5-HT) and dopamine reuptake inhibition. Sibutramine and its major pharmacologically active metabolites (M1 and M2) do not act via release of monoamines.||
Sibutramine Interacts with Diseases
|Disease||Inference Score||References/Inference Genes|
|Kidney Failure, Chronic||11.13||
|Drug Metabolism, Poor, CYP2C19-Related||6.38|
|Drug Metabolism, Poor, CYP2D6-Related||6.29|
|ADIPONECTIN, SERUM LEVEL OF, QUANTITATIVE TRAIT LOCUS 2||5.99||
|ADIPONECTIN, SERUM LEVEL OF, QUANTITATIVE TRAIT LOCUS 3||5.99||
|Primary ovarian insufficiency||5.18||
|Acute kidney injury||5.04||
|TOBACCO ADDICTION, SUSCEPTIBILITY TO||4.98||
|Metabolic Syndrome X||4.18||
|Sexual Dysfunctions, Psychological||4.13||