Nomifensine, formerly known as Merital capsules, is a dopamine reuptake inhibitor drug that was removed from the market in 1986 for increased incidence of hemolytic anemia. The drug was originally used to treat depression. Nomifensine stimulates the nervous system through the reuptake of norepinephrine 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 Nomifensine 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. Nomifensine 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.

Nomifensine Dopamine Reuptake Inhibitor Pathway References