Ephenidine and related diarylethylamines have been studied in vitro as treatments for neurotoxic injuries, and areantagonists of theNMDA receptor (Ki = 66.4 nM for ephenidine).[5][6][7][8][9] Ephenidine also possesses weaker affinity fordopamine andnorepinephrine transporters (379 nM and 841 nM, respectively) as well asσ1R (629 nM) andσ2R (722 nM) binding sites.[10]
Ephenidine'smetabolic pathway consists of N-oxidation, N-dealkylation, mono- and bis-hydroxylation of the benzyl ring, and hydroxylation of the phenyl ring only after N-dealkylation. The dihydroxy metabolites were conjugated by methylation of one hydroxy group, and hydroxy metabolites by glucuronidation or sulfation.[3][11]
Sweden's public health agency suggested that ephenidine be classified as a hazardous substance on 1 June, 2015. Due to that suggestion, ephenidine became a scheduled substance, in Sweden, as of 18 August, 2015.[13]
In 2016, Canada addedMT-45 and "its salts, derivatives, isomers and analogues" to the Schedule I controlled substance list, and explicitly included ephenidine.[14] Possession without legal authority can result in maximum 7 years imprisonment.
^Morris H, Wallach J (July–August 2014). "From PCP to MXE: a comprehensive review of the non-medical use of dissociative drugs".Drug Testing and Analysis.6 (7–8):614–32.doi:10.1002/dta.1620.PMID24678061.
^Meyer MR, Orschiedt T, Maurer HH (February 2013). "Michaelis-Menten kinetic analysis of drugs of abuse to estimate their affinity to human P-glycoprotein".Toxicology Letters.217 (2):137–42.doi:10.1016/j.toxlet.2012.12.012.PMID23273999.
^abWink CS, Meyer GM, Wissenbach DK, Jacobsen-Bauer A, Meyer MR, Maurer HH (October 2014). "Lefetamine-derived designer drugs N-ethyl-1,2-diphenylethylamine (NEDPA) and N-iso-propyl-1,2-diphenylethylamine (NPDPA): metabolism and detectability in rat urine using GC-MS, LC-MSn and LC-HR-MS/MS".Drug Testing and Analysis.6 (10):1038–48.doi:10.1002/dta.1621.PMID24591097.
^Wink CS, Meyer GM, Meyer MR, Maurer HH (November 2015). "Toxicokinetics of lefetamine and derived diphenylethylamine designer drugs-Contribution of human cytochrome P450 isozymes to their main phase I metabolic steps".Toxicology Letters.238 (3):39–44.doi:10.1016/j.toxlet.2015.08.012.PMID26276083.
^Berger ML, Schweifer A, Rebernik P, Hammerschmidt F (May 2009). "NMDA receptor affinities of 1,2-diphenylethylamine and 1-(1,2-diphenylethyl)piperidine enantiomers and of related compounds".Bioorganic & Medicinal Chemistry.17 (9):3456–62.doi:10.1016/j.bmc.2009.03.025.PMID19345586.
^Goodson LH, Wiegand CJ, Splitter JS (November 1946). "Analgesics; n-alkylated-1,2-diphenylethylamines prepared by the Leuckart reaction".Journal of the American Chemical Society.68 (11):2174–2175.Bibcode:1946JAChS..68.2174G.doi:10.1021/ja01215a018.PMID21002222.
^Wink CS, Meyer GM, Zapp J, Maurer HH (February 2015). "Lefetamine, a controlled drug and pharmaceutical lead of new designer drugs: synthesis, metabolism, and detectability in urine and human liver preparations using GC-MS, LC-MS(n), and LC-high resolution-MS/MS".Analytical and Bioanalytical Chemistry.407 (6):1545–57.doi:10.1007/s00216-014-8414-3.PMID25577353.S2CID26014465.
