4-Methylphenethylamine Explained

4-Methylphenethylamine (4MPEA), also known as para-methylphenethylamine, is an organic compound with the chemical formula of . 4MPEA is a human trace amine associated receptor 1 (TAAR1) agonist,^[1] a property which it shares with its monomethylated phenethylamine isomers, such as amphetamine (α-methylphenethylamine),, and (a trace amine). 4MPEA also appears to inhibit the human cytochrome P450 enzymes CYP1A2 and CYP2A6, based upon the published literature.^[2]

Notes and References

1. Wainscott DB, Little SP, Yin T, Tu Y, Rocco VP, He JX, Nelson DL . Pharmacologic characterization of the cloned human trace amine-associated receptor1 (TAAR1) and evidence for species differences with the rat TAAR1 . The Journal of Pharmacology and Experimental Therapeutics . 320 . 1 . 475–85 . January 2007 . 17038507 . 10.1124/jpet.106.112532 . 10829497 . Several series of substituted phenylethylamines were investigated for activity at the human TAAR1 (Table 2). A surprising finding was the potency of phenylethylamines with substituents at the phenyl C2 position relative to their respective C4-substituted congeners. In each case, except for the hydroxyl substituent, the C2-substituted compound had 8- to 27-fold higher potency than the C4-substituted compound. The C3-substituted compound in each homologous series was typically 2- to 5-fold less potent than the 2-substituted compound, except for the hydroxyl substituent. The most potent of the 2-substituted phenylethylamines was 2-chloro-β-PEA, followed by 2-fluoro-β-PEA, 2-bromo-β-PEA, 2-methoxy-β-PEA, 2-methyl-β-PEA, and then 2-hydroxy-β-PEA.
   The effect of β-carbon substitution on the phenylethylamine side chain was also investigated (Table 3). A β-methyl substituent was well tolerated compared with β-PEA. In fact, S-(−)-β-methyl-β-PEA was as potent as β-PEA at human TAAR1. β-Hydroxyl substitution was, however, not tolerated compared with β-PEA. In both cases of β-substitution, enantiomeric selectivity was demonstrated.
   In contrast to a methyl substitution on the β-carbon, an α-methyl substitution reduced potency by ~10-fold for d-amphetamine and 16-fold for l-amphetamine relative to β-PEA (Table 4). N-Methyl substitution was fairly well tolerated; however, N,N-dimethyl substitution was not..
2. Web site: 4-Methylphenethylamine . PubChem Compound . National Center for Biotechnology Information . 21 July 2014 .