Serotonin-norepinephrine specific agents

PEA and TYR are substrates for W-acetyltransferase (NAT)-mediated biotransformation process. NATs metabolize agents that contain an aromatic amine or hydrazine group. Addition of an acetyl group leads to a less soluble molecule, altering its pharmacokinetics [37]. Therefore, W-acetylation is used by cells as an inactivation process of excess amines. Substrate specificity of NAT for biogenic amines was investigated in Fasciola Hepatica. TYR and PEA were found to be the best substrates with a relative rate of 98-100 % as compared to serotonin, norepinephrine, and DOP [38]. 

The agents in this class demonstrate the common feature of specific inhibition of serotonin reuptake without significant effects on norepinephrine and dopamine reuptake. These agents also lack direct agonist or antagonist activity on any neurotransmitter receptor. 

Sibutramine, a novel pharmacologic agent, is a specific reuptake inhibitor for norepinephrine and serotonin. Sibutramine and its two metabolites reduce food intake and hence show promise as antiobesity medications. 

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