5-MeO-DMT-d4

Pharmaceutical compound From Wikipedia, the free encyclopedia

5-MeO-DMT-d4, also known as α,α,β,β-tetradeutero-5-MeO-DMT, is a serotonin receptor modulator and putative psychedelic drug of the tryptamine and 5-methoxytryptamine families related to 5-MeO-DMT.^[1]^[2]^[3] It is the isotopologue of 5-MeO-DMT in which the hydrogen atoms at the α and β positions have been replaced with the deuterium isotopes.^[1]^[3]

Other names[²H4]-5-MeO-DMT; α,α,β,β-Tetradeutero-5-MeO-DMT; α,α,β,β-Tetradeutero-5-methoxy-N,N-dimethyltryptamine

Drug classSerotonin receptor modulator; Serotonergic psychedelic; Hallucinogen

ATC code

None

CAS Number

66521-37-7

Quick facts Clinical data, Other names ...

5-MeO-DMT-d4
Clinical data

Other names	[²H4]-5-MeO-DMT; α,α,β,β-Tetradeutero-5-MeO-DMT; α,α,β,β-Tetradeutero-5-methoxy-N,N-dimethyltryptamine
Drug class	Serotonin receptor modulator; Serotonergic psychedelic; Hallucinogen
ATC code	None
Identifiers
IUPAC name 1,1,2,2-tetradeuterio-2-(5-methoxy-1H-indol-3-yl)-N,N-dimethylethanamine
CAS Number	66521-37-7
PubChem CID	25193910
ChemSpider	107437297
Chemical and physical data
Formula	C₁₃H₁₈N₂O
Molar mass	218.300 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES [2H]C([2H])(C1=CNC2=C1C=C(C=C2)OC)C([2H])([2H])N(C)C
InChI InChI=1S/C13H18N2O/c1-15(2)7-6-10-9-14-13-5-4-11(16-3)8-12(10)13/h4-5,8-9,14H,6-7H2,1-3H3/i6D2,7D2 Key:ZSTKHSQDNIGFLM-KXGHAPEVSA-N

Pharmacology

5-MeO-DMT-d4 shows similar affinities for serotonin receptors and other targets as 5-MeO-DMT.^[3] However, the drug is thought to be much more resistant to metabolism by monoamine oxidase (MAO) than 5-MeO-DMT, which in turn may result in greater potency and/or a longer duration.^[1]^[3] In addition, it may result in the drug becoming orally active, though this remains to be studied.^[1] It is known that monoamine oxidase inhibitors (MAOIs) with 5-MeO-DMT increase brain exposure to 5-MeO-DMT by approximately 20-fold in animals.^[2]^[4] 5-MeO-DMT-d4 showed similar effects on locomotor activity in rodents as a combination of 5-MeO-DMT and a MAOI.^[2]^[3]

Chemistry

Synthesis

The chemical synthesis of 5-MeO-DMT-d4 has been described.^[5]

History

5-MeO-DMT-d4 was first described in the scientific literature by 1977.^[6] Subsequently, it was described in greater detail by Adam Halberstadt and David E. Nichols and colleagues in 2012.^[1]^[3] The study of 5-MeO-DMT-d4 was preceded by that of DMT-d4 which was described in the 1980s.^[1]^[3]^[7]^[8]

References

[1]
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.
[2]
Halberstadt AL, Geyer MA (2018). "Effect of Hallucinogens on Unconditioned Behavior". Current Topics in Behavioral Neurosciences. 36: 159–199. doi:10.1007/7854_2016_466. ISBN 978-3-662-55878-2. PMC 5787039. PMID 28224459. Further work demonstrated that α,α,β,β-tetradeutero-5-MeO-DMT, a 5-MeO-DMT isotopologue that is resistant to metabolism by MAO, does not require an MAOI to produce a biphasic locomotor profile (Halberstadt et al. 2012). The latter finding indicates that MAOIs alter the behavioral profile of 5-MeO-DMT by slowing its biotransformation, which allows high levels of the drug to accumulate in the brain. Indeed, we found that the concentration of 5-MeO-DMT in the CNS is increased ~20-fold in animals pretreated with an MAOI (Halberstadt 2016).{{cite journal}}: CS1 maint: periodical has ISBN (link)
[3]
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.
[4]
Halberstadt AL (April 2016). "Behavioral and pharmacokinetic interactions between monoamine oxidase inhibitors and the hallucinogen 5-methoxy-N,N-dimethyltryptamine". Pharmacology, Biochemistry, and Behavior. 143: 1–10. doi:10.1016/j.pbb.2016.01.005. PMC 5403252. PMID 26780349.
[5]
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.
[6]
Shaw GJ, Wright GJ, Milne GW (December 1977). "Mass spectra of some specifically deuterated tryptamines". Biomedical Mass Spectrometry. 4 (6): 348–353. doi:10.1002/bms.1200040605. PMID 597583.
[7]
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.
[8]
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.

5-MeO-DMT-d4

Pharmacology

Chemistry

Synthesis

History

See also

References

Related Articles

Timelines

Top Qs

Fact Checks

Related Articles

"N, N-Dimethyltryptamine (DMT), an Endogenous Hallucinogen: Past, Present, and Future Research to Determine Its Role and Function"

"Effect of Hallucinogens on Unconditioned Behavior"

"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"

"Behavioral and pharmacokinetic interactions between monoamine oxidase inhibitors and the hallucinogen 5-methoxy-N,N-dimethyltryptamine"