Sibutramine, commonly known as Meridia or Reductil, is a norepinephrine, serotonin and dopamine reuptake inhibitor used for the treatment of obesity. This drug was withdrawn from US and Canadian markets for increased risk of heart attack and stroke in patients with heart disease history. Sibutramine stimulates the nervous system through the reuptake of norepinephrine, serotonin and dopamine, which prolongs their duration in the synapse so that they can bind more readily to the receptors. The mechanism is not fully understood, but may be similar to other dopamine reuptake inhibitors where Sibutramine would cross the blood-brain barrier through diffusion. Dopamine is synthesized in the ventral tegmental area of the brain from tyrosine being synthesized into L-dopa by the enzyme Tyrosine 3-monooxygenase . L-Dopa is then synthesized into dopamine with the enzyme aromatic-L-amino-acid decarboxylase. Dopamine then travels to the prefrontal cortex, which is released into the synapse when the neuron is stimulated and fires. Sibutramine binds to the sodium-dependent dopamine transporter, preventing dopamine from re-entering the presynaptic neuron. The dopamine then binds to Dopamine D4 receptors on the postsynaptic membrane. The dopamine D4 receptor activates the Gi protein cascade, which inhibits adenylate cyclase. This prevents adenylate cyclase from catalyzing ATP into cAMP.

Sibutramine Dopamine Reuptake Inhibitor Pathway References