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General chemical structure of a diarylethylamine

Diarylethylamines are a chemical class of psychoactive substances that produce dissociative effects when administered. Subjective effects are similar to those of arylcyclohexylamine dissociatives like PCP or ketamine, although they differ in their chemical structure.

Diarylethylamines are examples of contemporary designer drugs specifically chosen to mimic and/or replace the functional and structural features of commonly used illicit substances. They have been marketed on the online research chemicals market as a replacement for MXE and other dissociatives.

Very little is known about the human pharmacology, metabolism, and toxicity of these compounds. Many reports suggest that they may pose different and more pronounced risks than traditional dissociatives.


NMDAR binding affinities for five target 1,2-diphenylethylamines and reference compounds[1]
Compound IC50 ± SEM (nM) Ki ± SEM (nM)
PCP[2] 91 ± 1.3 57.9 ± 0.8
Ketamine 508.5 ± 30.1 323.9 ± 19.2
Memantine 594.2 ± 41.3 378.4 ± 26.3
(+)-MK-801 4.1 ± 1.6 2.5 ± 1.0
Diphenidine* 28.6 ± 3.5 18.2 ± 2.2
2-MXP (Methoxphenidine) 56.5 ± 5.8 36.0 ± 3.7
3-MXP 30.3 ± 2.6 19.3 ± 1.7
4-MXP 723.8 ± 69.9 461.0 ± 44.5
2-Cl-Diphenidine* 14.6 ± 2.1 9.3 ± 1.3
NMDAR binding affinites determined using [3H]-(+)-MK-801 in rat forebrain.[3]

*Diphenidine is sometimes referred to as DPH in scientific studies despite this name already being in common use and widely accepted as meaning diphenhydramine, an unrelated substance.

List of substituted diarylethylamines

Compound RN1 RN2 R2 Structure
Ephenidine CH2CH3 H H Ephenidine.svg
Diphenidine CH2CH2CH2- CH2CH2- H Diphenidine.svg
Methoxphenidine CH2CH2CH2- CH2CH2- OCH3 Methoxphenidine.svg

See also


  • Wallach, J., Kang, H., Colestock, T., Morris, H., Bortolotto, Z. A., Collingridge, G. L., ... & Adejare, A. (2016). Pharmacological investigations of the dissociative ‘legal highs’ diphenidine, methoxphenidine and analogues. PLoS One, 11(6), e0157021. https://doi.org/10.1371/journal.pone.0157021
  • Morris, H., & Wallach, J. (2014). From PCP to MXE: A comprehensive review of the non-medical use of dissociative drugs. Drug Testing and Analysis, 6(7–8), 614–632. https://doi.org/10.1002/dta.1620
  • Wallach, J., & Brandt, S. D. (2018). 1, 2-Diarylethylamine-and Ketamine-Based New Psychoactive Substances. In New Psychoactive Substances (pp. 305-352). Springer, Cham. http://dx.doi.org/10.1007/164_2018_148