α,α-Dideuterophenethylamine
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| Other names | α,α-Dideutero-phenethylamine; α,α-Dideutero-2-phenylethylamine; PE-α,α-d2; D2PE |
| Drug class | Monoamine releasing agent |
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| Formula | C8H11N |
| Molar mass | 121.183 g·mol−1 |
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α,α-Dideuterophenethylamine, also known as PE-α,α-d2 or D2PE, is a deuterated isotopologue of phenethylamine.[1][2][3][4][5] It is the analogue of phenethylamine in which the two hydrogen atoms at the α position have been replaced with the deuterium isotopes.[2][3][4][5]
Pharmacology
α,α-Dideuterophenethylamine showed considerably reduced deamination by monoamine oxidase (MAO) compared to phenethylamine in vitro.[1][4] Conversely, β,β-dideuterophenethylamine was not resistant to metabolism by MAO relative to phenethylamine in vitro.[1][4] Similarly, levels of α,α-dideuterophenethylamine were 16-fold higher in the brain, 2.4-fold higher in the liver, and 4.3-fold higher in plasma than levels of phenethylamine after 30 minutes when both drugs were administered via intraperitoneal injection in rodents.[5][2] In contrast, β,β-dideuterophenethylamine showed no differences from phenethylamine in such regards.[5][2]
On the other hand, another deuterated isotopologue of phenethylamine, α,α,β,β-tetradeuterophenethylamine, showed brain levels that were 10-fold higher than those of phenethylamine after 30 minutes and 67-fold higher than phenethylamine after 60 minutes in rodents, whereas levels were no longer different between the two drugs at 120 minutes (i.e., 1.0 ratio).[5][3] Likewise, α,α,β,β-tetradeuterophenethylamine showed enhanced levels in the liver and plasma compared to phenethylamine, albeit to a much lesser extent of only 3- to 4-fold.[5] The differences in levels of α,α,β,β-tetradeuterophenethylamine versus phenethylamine in the brain were markedly reduced by pretreatment with the monoamine oxidase inhibitor (MAOI) pargyline, for instance diminishing them at 60 minutes from 67-fold to only 11-fold.[5] These findings suggest that reduced metabolism by MAO was largely but not fully responsible for the enhanced levels of α,α,β,β-tetradeuterophenethylamine compared to phenethylamine, although it was noted that MAO inhibition by pargyline was probably incomplete and hence could also have been involved.[5]
Like phenethylamine, α,α-dideuterophenethylamine has been found to be a dopamine releasing agent in rodents in vivo, but given at the same dose, showed greater magnitude of effect and longer-lasting effects.[6] α,α-Dideuterophenethylamine fully substituted for phenethylamine in rodent drug discrimination tests, with about 1.5- to 2.2-fold greater potency in comparison.[7] The related deuterated isotopologue α,α,β,β-tetradeuterophenethylamine has also been studied in terms of behavioral effects in rodents and was found to produce greater intensity and duration of hyperlocomotion than phenethylamine when given at the same dose.[8] Its duration was extended by 33% compared to phenethylamine.[8]
The urinary excretion of "phenylethylamine-d2" (deuteration specifics not described) in a human male has been studied.[9][10] It was given as a single 500 mg dose orally.[9][10] The effects of the drug were not described.[9][10]
History
α,α-Dideuterophenethylamine was first described in the scientific literature by 1981.[4] It was then further studied and described throughout the rest of the 1980s.[1][2][3][5][6] α,α,β,β-Tetradeuterophenethylamine was likewise studied and described in the 1980s.[5][3][8]
See also
- Substituted phenethylamine
- α,α-Dideuterotryptamine
- α,α-Dideuteromescaline
- HLP005 (likely deuterated 2C-T-36)
- d2-MDMA
- N-(2-Cyanoethyl)phenethylamine (CEPEA or CE-PEA)
References
- 1 2 3 4 Boulton AA, Juorio AV, Paterson IA (1990). "Phenylethylamine in the CNS: Effects of monoamine oxidase inhibiting drugs, deuterium substitution and lesions and its role in the neuromodulation of catecholaminergic neurotransmission". Neurotransmitter Actions and Interactions. Vol. 29. pp. 119–129. doi:10.1007/978-3-7091-9050-0_12. ISBN 978-3-211-82142-8. PMID 2193105.
{{cite book}}:|journal=ignored (help) - 1 2 3 4 5 Dyck LE, Davis BA, Durden DA, Boulton AA (1985). "Potentiation of the Biochemical Effects of β-Phenylethylamine and Tryptamine by Deuterium Substitution". Neuropsychopharmacology of the Trace Amines. Totowa, NJ: Humana Press. pp. 75–86. doi:10.1007/978-1-4612-5010-4_7. ISBN 978-1-4612-9397-2. Retrieved 28 May 2026.
- 1 2 3 4 5 Boulton AA (1985). "The Trace Amines: Recent Overview and Future Pointers". Neuropsychopharmacology of the Trace Amines. Totowa, NJ: Humana Press. pp. 3–12. doi:10.1007/978-1-4612-5010-4_1. ISBN 978-1-4612-9397-2. Retrieved 28 May 2026.
- 1 2 3 4 5 Yu PH, Barclay S, Davis B, Boulton AA (November 1981). "Deuterium isotope effects on the enzymatic oxidative deamination of trace amines". Biochemical Pharmacology. 30 (22): 3089–3094. doi:10.1016/0006-2952(81)90497-4. PMID 7337725.
- 1 2 3 4 5 6 7 8 9 10 Dyck LE, Durden DA, Boulton AA (February 1986). "Effects of deuterium substitution on the catabolism of beta-phenylethylamine: an in vivo study". Journal of Neurochemistry. 46 (2): 399–404. doi:10.1111/j.1471-4159.1986.tb12982.x. PMID 3941313.
- 1 2 Philips SR (December 1986). "In vivo release of endogenous dopamine from rat caudate nucleus by beta-phenylethylamine and alpha,alpha,-dideutero-beta-phenylethylamine". Life Sciences. 39 (25): 2395–2400. doi:10.1016/0024-3205(86)90480-7. PMID 3796200.
- ↑ Reid D, Goudie AJ (June 1986). "Discriminative stimulus properties of beta-phenylethylamine, deuterated beta-phenylethylamine, phenylethanolamine and some metabolites of phenylethylamine in rodents". Pharmacology, Biochemistry, and Behavior. 24 (6): 1547–1453. doi:10.1016/0091-3057(86)90483-1. PMID 3737623.
- 1 2 3 Dourish CT, Greenshaw AJ, Boulton AA (September 1983). "Deuterium substitution enhances the effects of beta-phenylethylamine on spontaneous motor activity in the rat". Pharmacology, Biochemistry, and Behavior. 19 (3): 471–475. doi:10.1016/0091-3057(83)90122-3. PMID 6634898.
- 1 2 3 Davis BA, Boulton AA (1980). "Urinary excretion of labeled metabolites following ingestion of deuterated phenylethylamine in a human male (Abstracts of Third Annual Meeting of Canadian Congress of Neuropsychopharmacology)" (PDF). Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques. 7 (3): 227–241 (231–231). doi:10.1017/S0317167100023258. ISSN 0317-1671.
- 1 2 3 Davis BA, Boulton AA (1980). "The metabolism of ingested deuterated β-phenylethylamine in a human male". Eur. J. Mass Spectrom. Biochem. Med. Environ. Res. 1: 149–153.