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4-Methoxyphenethylamine

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4-Methoxyphenethylamine
Clinical data
Other names4-MPEA; para-Methoxyphenethylamine; p-Methoxyphenethylamine; PMPEA; O-Methyltyramine; Methyltyramine; Tyramine methyl ether; Homoanisylamine; NSC-43687
Drug classMonoamine releasing agent
ATC code
  • None
Identifiers
  • 2-(4-methoxyphenyl)ethanamine
CAS Number
PubChem CID
ChemSpider
UNII
ChEBI
ChEMBL
Chemical and physical data
FormulaC9H13NO
Molar mass151.209 g·mol−1
3D model (JSmol)
  • COC1=CC=C(C=C1)CCN
  • InChI=1S/C9H13NO/c1-11-9-4-2-8(3-5-9)6-7-10/h2-5H,6-7,10H2,1H3
  • Key:LTPVSOCPYWDIFU-UHFFFAOYSA-N

4-Methoxyphenethylamine (4-MPEA), also known as O-methyltyramine, is a drug of the phenethylamine family.[1][2][3][4] It is one of the methoxyphenethylamine positional isomers.[1][3] Along with mescaline (3,4,5-trimethoxyphenethylamine), 4-MPEA is naturally occurring in Lophophora williamsii (peyote) and other cacti.[1] It has also been found in the flowering plant Erica lusitanica, as well as in human urine.[1][2]

Use and effects

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4-MPEA was inactive in humans at a dose of up to 400 mg.[1][3][4][2][5][6][7]

Pharmacology

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4-MPEA has been found to act as a serotonin releasing agent and norepinephrine releasing agent in vitro.[1][8][9][10][11] It has also been found to be very weakly active as a dopamine reuptake inhibitor, whereas dopamine release induction does not appear to have been assessed.[1][12] The drug showed very low affinity for the serotonin receptors in the rat stomach fundus strip (A2 = 7,940 nM).[1][13] 4-MPEA is a very-low-potency partial agonist of the human trace amine-associated receptor 1 (TAAR1) (EC50Tooltip half-maximal effective concentration = 5,980 nM; EmaxTooltip maximal efficacy = 106%).[14]

In animals, 4-MPEA produced catalepsy, catatonia, a hypokinetic rigid syndrome, and indirect sympathomimetic effects, among other effects.[1][2][15]

The drug is metabolized by monoamine oxidase (MAO), specifically monoamine oxidase B (MAO-B).[1][16][17] It is thought to be rapidly metabolized by MAO such that it is rendered inactive.[18]

History

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4-MPEA was first described in the scientific literature by at least 1931.[19][20][21][22][1] It was included as an entry in Alexander Shulgin's 2011 book The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds.[1]

See also

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References

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  1. ^ a b c d e f g h i j k l Shulgin A, Manning T, Daley PF (2011). "#102. 4-MPEA". The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds. Vol. 1. Berkeley, CA: Transform Press. pp. 245–249. ISBN 978-0-9630096-3-0. OCLC 709667010.
  2. ^ a b c d Shulgin AT (1978). "Psychotomimetic Drugs: Structure-Activity Relationships". Stimulants. Boston, MA: Springer US. pp. 243–333. doi:10.1007/978-1-4757-0510-2_6. ISBN 978-1-4757-0512-6. 2.1.4. 4-Methoxyphenethylamine: Interest has been directed toward the simpler methoxylated phenethylamines for a number of years. Ernst (1962, 1965) had observed that the lower homologs of mescaline, 4-methoxyphenethylamine (14, MPEA) and DMPEA (6) produced a mescaline-like catatonia in mice, a property that is absent in the corresponding phenols. Michaux and Verly (1963) reported that the mono-methoxy compound (14) was the most biologically active of these methoxylated phenethylamines. MPEA (14) as well as DMPEA (6) has been found as a component of human urine (Sen and McGeer, 1964). Brown et at. (1968) have studied the effects of MPEA in man. Sixteen normal subjects were given MPEA at dose levels of approximately 400 mg orally, employing mescaline as a standard in the same subjects, and at the same dose. All of the subjects reacted as expected to the mescaline administration, and none of them showed any response whatsoever to MPEA.
  3. ^ a b c Shulgin A, Shulgin A (September 1991). PiHKAL: A Chemical Love Story. Berkeley, California: Transform Press. ISBN 0-9630096-0-5. OCLC 25627628. "The 2-carbon analog of 4-MA, is 4-methoxyphenethylamine, or MPEA. This is a kissing cousin to DMPEA, of such fame in the search for a urine factor that could be related to schizophrenia. And the end results of the search for this compound in the urine of mentally ill patients are as controversial as they were for DMPEA. There has been no confirmed relationship to the diagnosis. And efforts to see if it is centrally active were failures—at dosages of up to 400 milligrams in man, there was no activity."
  4. ^ a b Brimblecombe RW, Pinder RM (1975). "Phenylalkylamines and Their Derivatives". Hallucinogenic Agents. Bristol: Wright-Scientechnica. pp. 55–97. Table 3.2.—RELATIVE HALLUCINOGENIC POTENCIES OF SOME PHENYLETHYLAMINES [...]
  5. ^ Braun U, Braun G, Jacob P, Nichols DE, Shulgin AT (1978). "Mescaline analogs: substitutions at the 4-position". NIDA Research Monograph (22): 27–37. PMID 101882.
  6. ^ Brown WT, McGeer PL, Moser I (February 1968). "Lack of psychotomimetic effect of para-methoxyphenylethylamine and 3,4-dimethoxyphenethylamine in man". Canadian Psychiatric Association Journal. 13 (1): 91–92. doi:10.1177/070674376801300117. PMID 5644428.
  7. ^ Shulgin AT, Sargent T, Naranjo C (February 1969). "Structure--activity relationships of one-ring psychotomimetics". Nature. 221 (5180): 537–541. Bibcode:1969Natur.221..537S. doi:10.1038/221537a0. PMID 5789297.
  8. ^ Biel JH, Bopp BA (1978). "Amphetamines: Structure-Activity Relationships". Stimulants. Boston, MA: Springer US. pp. 1–39. doi:10.1007/978-1-4757-0510-2_1. ISBN 978-1-4757-0512-6. Retrieved 3 July 2025.
  9. ^ Hwang EC, Van Woert MH (March 1979). "Behavioral and biochemical effects of para-methoxyphenylethylamine". Research Communications in Chemical Pathology and Pharmacology. 23 (3): 419–431. PMID 461968.
  10. ^ Chung Hwang E, Van Woert MH (May 1980). "Comparative effects of substituted phenylethylamines on brain serotonergic mechanisms". The Journal of Pharmacology and Experimental Therapeutics. 213 (2): 254–260. doi:10.1016/S0022-3565(25)32053-7. PMID 6965983.
  11. ^ Daly JW, Creveling CR, Witkop B (May 1966). "The chemorelease of norepinephrine from mouse hearts. Structure-activity relationships. I. Sympathomimetic and related amines". Journal of Medicinal Chemistry. 9 (3): 273–280. doi:10.1021/jm00321a001. PMID 5960887.
  12. ^ Horn AS (February 1973). "Structure-activity relations for the inhibition of catecholamine uptake into synaptosomes from noradrenaline and dopaminergic neurones in rat brain homogenates". British Journal of Pharmacology. 47 (2): 332–338. doi:10.1111/j.1476-5381.1973.tb08331.x. PMC 1776552. PMID 4722047.
  13. ^ Glennon RA, Liebowitz SM, Anderson GM (March 1980). "Serotonin receptor affinities of psychoactive phenalkylamine analogues". Journal of Medicinal Chemistry. 23 (3): 294–299. doi:10.1021/jm00177a017. PMID 7365744.
  14. ^ Lewin AH, Navarro HA, Mascarella SW (August 2008). "Structure-activity correlations for beta-phenethylamines at human trace amine receptor 1". Bioorganic & Medicinal Chemistry. 16 (15): 7415–7423. doi:10.1016/j.bmc.2008.06.009. PMC 2601700. PMID 18602830.
  15. ^ Cession-Fossion A (1963). "La P-Methoxy-Phenylethylamine (O-Methyltyramine) Agit Comme Amine Sympathicomim'etique Indirecte" [P-Methoxyphenylethylamine (O-Methyltyramine) Acts Like an Indirect Sympathicomimetic Amine]. Comptes Rendus des Seances de la Societe de Biologie et de Ses Filiales (in French). 157: 1835–1838. PMID 14111699.
  16. ^ Suzuki O, Matsumoto T, Katsumata Y, Oya M (1980). "Methoxyphenylethylamines as substrates for type A and type B monoamine oxidase". Experientia. 36 (8): 895–897. doi:10.1007/BF01953778. ISSN 0014-4754. Retrieved 3 July 2025.
  17. ^ Willis Jr WD, Ashkenazi R, Willis JC, Haber B (1973). "Role of monoamine oxidase in terminating the reflex effects of p-methoxyphenylethylamine (PMPEA)". Texas Reports on Biology and Medicine. 31 (3): 423–429.
  18. ^ Vogel WH, Evans BD (May 1977). "Structure-activity-relationships of certain hallucinogenic substances based on brain levels". Life Sciences. 20 (10): 1629–1635. doi:10.1016/0024-3205(77)90335-6. PMID 69244. It has been claimed that 4-methoxyphenylethylamine might be a paradigm hallucinogenic substance and the lack of behavioral activity at the lower doses is due to the rapid metabolism and to the inability of the compound to accumulate in the brain.
  19. ^ Jansen MP (1931). "β-2: 4: 5-Trimethoxyphenylethylamine, an isomer of mescaline". Recueil des Travaux Chimiques des Pays-Bas. 50 (4): 291–312. doi:10.1002/recl.19310500403. ISSN 0165-0513. Retrieved 3 July 2025.
  20. ^ Hjort AM, Debeer EJ, Buck JS, Randall LO (1942). "Relative pharmacological effects of 1-methyl-3,4-dihydro-and 1-methyl-1,2,3,4-tetrahydroisoquinoline derivatives". The Journal of Pharmacology and Experimental Therapeutics. 76 (3): 263–269. doi:10.1016/S0022-3565(25)10046-3.
  21. ^ Alles GA, Heegaard EV (1943). "Substrate specificity of amine oxidase". Journal of Biological Chemistry. 147 (3): 487–503. doi:10.1016/S0021-9258(18)72344-2.
  22. ^ Clark LC, Benington F, Morin RD (May 1965). "The effects of ring-methoxyl groups on biological deamination of phenethylamines". Journal of Medicinal Chemistry. 8 (3): 353–355. doi:10.1021/jm00327a016. PMID 14323146.
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