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| Other names | D4DMT; [2H4]-DMT; Dimethyltryptamine-d4; α,α,β,β-Tetradeutero-DMT; α,α,β,β-Tetradeutero-N,N-dimethyltryptamine |
| Drug class | Serotonin receptor modulator; Serotonergic psychedelic; Hallucinogen |
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| Formula | C12H16N2 |
| Molar mass | 188.274 g·mol−1 |
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DMT-d4, or D4DMT, also known as α,α,β,β-tetradeutero-DMT, is a serotonin receptor modulator and putative psychedelic drug of the tryptamine family related to dimethyltryptamine (DMT).[1][2][3][4] It is the isotopologue of DMT in which the hydrogen atoms at the α and β positions have been replaced with the deuterium isotopes.[1][2][3][4]
Pharmacology
[edit]DMT-d4 is thought to be resistant to metabolism by monoamine oxidase (MAO) compared to DMT.[1][2][3][4] Relatedly, D4DMT, at the same dose, shows stronger effects, 2- to 3-fold higher brain levels, a longer duration, and a faster onset than DMT in rodents.[1][2][3][4] In addition, DMT-d4, unlike DMT, might be orally active, though this remains to be studied.[1] D4DMT was said to have similar properties to the combination of DMT with a monoamine oxidase inhibitor (MAOI) in rodents.[1][2][4] The metabolism and metabolites of DMT-d4 have been studied.[4]
Chemistry
[edit]Synthesis
[edit]The chemical synthesis of DMT-d4 has been described.[5]
Analogues
[edit]A notable analogue of DMT-d4 is 5-MeO-DMT-d4.[1][6] Other analogues of DMT-d4 include deuterated forms of tryptamine like α,α-dideuterotryptamine and β,β-dideuterotryptamine.[7][8][9][10]
History
[edit]DMT-d4 was first described in the scientific literature by 1982.[1][2][3][4]
See also
[edit]References
[edit]- ^ a b c d e f g h Barker SA (2018). "N, N-Dimethyltryptamine (DMT), an Endogenous Hallucinogen: Past, Present, and Future Research to Determine Its Role and Function". Frontiers in Neuroscience. 12 536. doi:10.3389/fnins.2018.00536. PMC 6088236. PMID 30127713.
In 1982, Beaton et al., reported on the behavioral effects of DMT and α,α,β,β-tetradeutero-DMT (9, Figure 3; D4DMT) administered interperitoneally to rats at a dose level of 2.5 and 5.0 mg/kg. The D4DMT was observed to produce, at equivalent doses to DMT itself, a significantly greater disruption of behavior, a longer duration of action and a shorter time to onset than non-deuterated DMT. This potentiation was apparently due to the kinetic isotope effect which, in theory, makes it harder for the MAO enzyme to extract a deuterium (vs. a hydrogen) from the alpha position (Figure 3), thus inhibiting degradation by MAO. In a companion study, Barker et al. (1982) also showed that, at the same dose, D4DMT attained a significantly higher brain concentration than DMT itself and that the elevation in brain level lasted for a longer period of time. Similar data have recently been presented for a tetra deutero-5-MeO-DMT (Halberstadt et al., 2012) and the authors reached a similar conclusion; these results demonstrate that deuterated tryptamines may be useful in behavioral and pharmacological studies to mimic the effects of tryptamine/MAOI combinations, but without the MAOI. While the synthesis of deuterated analogs may be more expensive initially, newer methods for such synthesis (Brandt et al., 2008) may overcome these concerns. Furthermore, the pharmacological properties of D4DMT may render it orally active. Such a possibility has yet to be explored. It is also possible that oral administration and kinetic isotope effect inhibition of metabolism may prolong the effects of a deuterated analog sufficiently to also be of use in imaging studies.
- ^ a b c d e f Beaton JM, Barker SA, Liu WF (May 1982). "A comparison of the behavioral effects of proteo-and deutero-N, N-dimethyltryptamine". Pharmacology, Biochemistry, and Behavior. 16 (5): 811–814. doi:10.1016/0091-3057(82)90240-4. PMID 6806829.
- ^ a b c d e Barker SA, Beaton JM, Christian ST, Monti JA, Morris PE (August 1982). "Comparison of the brain levels of N,N-dimethyltryptamine and alpha, alpha, beta, beta-tetradeutero-N-N-dimethyltryptamine following intraperitoneal injection. The in vivo kinetic isotope effect". Biochemical Pharmacology. 31 (15): 2513–2516. doi:10.1016/0006-2952(82)90062-4. PMID 6812592.
- ^ a b c d e f g Barker SA, Beaton JM, Christian ST, Monti JA, Morris PE (May 1984). "In vivo metabolism of alpha,alpha,beta,beta-tetradeutero-N, N-dimethyltryptamine in rodent brain". Biochemical Pharmacology. 33 (9): 1395–1400. doi:10.1016/0006-2952(84)90404-0. PMID 6587850.
- ^ Brandt SD, Tirunarayanapuram SS, Freeman S, Dempster N, Barker SA, Daley PF, et al. (2008). "Microwave-accelerated synthesis of psychoactive deuterated N , N -dialkylated-[ α , α , β , β -d 4 ]-tryptamines" (PDF). Journal of Labelled Compounds and Radiopharmaceuticals. 51 (14): 423–429. doi:10.1002/jlcr.1557. ISSN 0362-4803.
- ^ Halberstadt AL, Nichols DE, Geyer MA (June 2012). "Behavioral effects of α,α,β,β-tetradeutero-5-MeO-DMT in rats: comparison with 5-MeO-DMT administered in combination with a monoamine oxidase inhibitor". Psychopharmacology. 221 (4): 709–718. doi:10.1007/s00213-011-2616-6. PMC 3796951. PMID 22222861.
It is well established that α-deutero substitution in the ethylamine side chain of tryptamines induces resistance to metabolism by MAO via the kinetic isotope effect (Beaton et al. 1982; Barker et al. 1982, 1984; Dyck and Boulton 1986). Indeed, after α,α,β,β-tetradeuteration of DMT, higher brain levels are achieved and clearance time is increased (Barker et al. 1982).
- ^ Dyck LE, Boulton AA (September 1986). "Effect of deuterium substitution on the disposition of intraperitoneal tryptamine". Biochemical Pharmacology. 35 (17): 2893–2896. doi:10.1016/0006-2952(86)90482-x. PMID 3741480.
- ^ 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 24 February 2026.
- ^ Durden DA, Nguyen TV, Boulton AA (October 1988). "Kinetics of intraventricularly injected trace amines and their deuterated isotopomers". Neurochemical Research. 13 (10): 943–950. doi:10.1007/BF00970766. PMID 3216952.
- ^ Belleau B, Burba J, Pindell M, Reiffenstein J (January 1961). "Effect of Deuterium Substitution in Sympathomimetic Amines on Adrenergic Responses". Science. 133 (3446): 102–104. doi:10.1126/science.133.3446.102. PMID 17769335.