N-Methylphenethylamine

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N-Methylphenethylamine[1]
N-methylphenethylamine2DCSD.svg
N-Methylphenethylamine molecule ball.png
Names
IUPAC name
N-Methyl-2-phenylethanamine
Other names
N-Methylphenethylamine
N-Methyl-β-phenethylamine
Identifiers
589-08-2
ChEMBL ChEMBL45763 YesY
ChemSpider 11019 YesY
Jmol 3D model Interactive image
PubChem 11503
  • InChI=1S/C9H13N/c1-10-8-7-9-5-3-2-4-6-9/h2-6,10H,7-8H2,1H3 YesY
    Key: SASNBVQSOZSTPD-UHFFFAOYSA-N YesY
  • InChI=1/C9H13N/c1-10-8-7-9-5-3-2-4-6-9/h2-6,10H,7-8H2,1H3
    Key: SASNBVQSOZSTPD-UHFFFAOYAA
  • N(CCc1ccccc1)C
Properties
C9H13N
Molar mass 135.21 g·mol−1
Appearance Colorless liquid
Density 0.93 g/mL
Boiling point 203 °C (397 °F; 476 K)
Vapor pressure {{{value}}}
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
YesY verify (what is YesYN ?)
Infobox references

N-Methylphenethylamine (NMPEA), a positional isomer of amphetamine,[2] is a naturally occurring trace amine neuromodulator in humans that is derived from the trace amine, phenethylamine (PEA).[3][4] It has been detected (< 1 μg/24 hrs.) in human urine[5] and is produced by phenylethanolamine N-methyltransferase with phenethylamine as a substrate.[3][4] PEA and NMPEA are both alkaloids that are found in a number of different plant species as well.[6] Some Acacia species, such as A. rigidula, contain remarkably high levels of NMPEA (~2300–5300 ppm).[7] NMPEA is also present at low concentrations (< 10 ppm) in a wide range of foodstuffs.[8]

Human biosynthesis pathway for trace amines and catecholamines[4][9]
The image above contains clickable links
N-methylphenethylamine, an endogenous compound in humans,[4] is an isomer of amphetamine with the same biomolecular target, TAAR1, a G protein-coupled receptor which modulates catecholamine neurotransmission.[10]

Chemistry

In appearance, NMPEA is a colorless liquid. NMPEA is a weak base, with pKa = 10.14; pKb = 3.86 (calculated from data given as Kb[11]). It forms a hydrochloride salt, m.p. 162–164°C.[12]

Although NMPEA is available commercially, it may be synthesized by various methods. An early synthesis reported by Carothers and co-workers involved conversion of phenethylamine to its p-toluenesulfonamide, followed by N-methylation using methyl iodide, then hydrolysis of the sulfonamide.[11] A more recent method, similar in principle, and used for making NMPEA radio-labeled with 14C in the N-methyl group, started with the conversion of phenethylamine to its trifluoroacetamide. This was N-methylated (in this particular case using 14C – labeled methyl iodide), and then the amide hydrolyzed.[13]

NMPEA is a substrate for both MAO-A (KM = 58.8 μM) and MAO-B (KM = 4.13 μM) from rat brain mitochondria.[14]

Pharmacology

NMPEA is a pressor, with 1/350 x the potency of epinephrine.[15]

Like its parent compound, PEA, and isomer, amphetamine, NMPEA is a potent agonist of human TAAR1.[4][9] It has comparable pharmacodynamic and toxicodynamic properties to that of phenethylamine, amphetamine, and other methylphenethylamines in rats.[2]

As with PEA, NMPEA is metabolized relatively rapidly by monoamine oxidases during first pass metabolism;[4][9] both compounds are preferentially metabolized by MAO-B.[4][9]

Toxicology

The "minimum lethal dose" (mouse, i.p.) of the HCl salt of NMPEA is 203 mg/kg;[16] the LD50 for oral administration to mice of the same salt is 685 mg/kg.[17]

Acute toxicity studies on NMPEA show an LD50 = 90 mg/kg, after intravenous administration to mice.[18]

References

  1. N-Methyl-phenethylamine at Sigma-Aldrich
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  5. G. P. Reynolds and D. O. Gray (1978) J. Chrom. B: Biomedical Applications 145 137–140.
  6. T. A. Smith (1977). "Phenethylamine and related compounds in plants." Phytochem. 16 9–18.
  7. B. A. Clement, C. M. Goff and T. D. A. Forbes (1998) Phytochem. 49 1377–1380.
  8. G. B. Neurath et al. (1977) Fd. Cosmet. Toxicol. 15 275–282.
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  11. 11.0 11.1 W.H. Carothers, C. F. Bickford and G. J. Hurwitz (1927) J. Am. Chem. Soc. 49 2908–2914.
  12. C. Z. Ding et al. (1993) J. Med. Chem. 36 1711–1715.
  13. I. Osamu (1983) Eur. J. Nucl. Med. 8 385–388.
  14. O. Suzuki, M. Oya and Y. Katsumata (1980) Biochem. Pharmacol. 29 2663–2667.
  15. W. H. Hartung (1945) Ind. Eng. Chem. 37 126–137.
  16. A. M. Hjort (1934) J. Pharm. Exp. Ther. 52 101–112.
  17. C. M. Suter and A. W. Weston (1941) J. Am. Chem. Soc. 63 602–605.
  18. A. M. Lands and J. I. Grant (1952). "The vasopressor action and toxicity of cyclohexylethylamine derivatives." J. Pharmacol. Exp. Ther. 106 341–345.