Metanephrine is an endogenous metabolite of ephinephrine, formed by catechol-O-methyl transferase activity. It is best known as a biomarker for cancers, as levels of free metanephrine are used to diagnose pheochromocytoma. Metanephrine was previously thought to be biologically inactive, but it is a more potent agonist at Trace amine associated receptor TAAR1 than either epinephrine or norepinephrine. Trace amine associated receptors (TAARs) are recently discovered GPCRs that are activated by endogenous trace amines (tyramine, tryptamine, synephrine, octopamine, β-phenylethylamine), which are chemically similar to monoaminergic neurotransmitters (epinephrine, norepinephrine, dopamine). Trace amines and TAARs are expressed in brain and are implicated in modulation of monoaminergic neurotransmission.
