Alpha-D
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| Clinical data | |
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| Other names | α-D; α,α-Dideuteromescaline; 3,4,5-Trimethoxy-α,α-dideuterophenethylamine; α,α-Dideutero-3,4,5-trimethoxyphenethylamine |
| Routes of administration | Oral[1] |
| Drug class | Serotonergic psychedelic; Hallucinogen |
| ATC code |
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| Pharmacokinetic data | |
| Onset of action | Unknown[1][2] |
| Duration of action | Unknown[1][2] |
| Identifiers | |
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| PubChem CID | |
| Chemical and physical data | |
| Formula | C11H17NO3 |
| Molar mass | 211.261 g·mol−1 |
| 3D model (JSmol) | |
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Alpha-D, or α-D, also known as 3,4,5-trimethoxy-α,α-dideuterophenethylamine or as α,α-dideuteromescaline, is a psychedelic drug of the phenethylamine and scaline families related to mescaline.[2][1][3][4] It is the isotopologue of mescaline in which the two hydrogen atoms at the α position have been replaced with the deuterium isotopes.[2][1][3][4]
According to Alexander Shulgin in his book PiHKAL (Phenethylamines I Have Known and Loved) and other publications, α-D had not yet been synthesized or tested, but would be expected to have similar properties and effects to those of mescaline.[2][3][4] However, it would be expected to have reduced metabolism via deamination than mescaline, which may result in some degree of greater potency in comparison.[2][3][4] Subsequently, Daniel Trachsel reported in his book Phenethylamine: von der Struktur zur Funktion (Phenethylamines: From Structure to Function), based on anonymous personal communication in 2009, that α-D is active at a dose of 230 mg orally, with substantial effects similar to those of a 320 mg dose of mescaline in the same subject.[1] As such, α-D may be approximately one-third more potent than mescaline.[1] This is consistent with approximately one-third of a dose of mescaline being excreted as the deaminated inactive metabolite 3,4,5-trimethoxyphenylacetic acid (TMPAA) in humans.[1][5][6]
The chemical synthesis of α-D has been described.[2][1] Analogues of α-D include β-D (beta-D; β,β-dideuteromescaline), α,β-D (alpha,beta-D; α,β-dideuteromescaline), and 4-D (4-trideuteromescaline), among others.[2][1][3][4]
α-D was described by Shulgin in PiHKAL in 1991 and in subsequent publications.[2][3][4] Later, Trachsel further described α-D and its properties in humans in 2013.[1] The drug does not seem to be a controlled substance in Canada as of 2025.[7]
See also
[edit]- Scaline
- β-D (β,β-dideuteromescaline)
- α,β-D (α,β-dideuteromescaline)
- 4-D (4-trideuteromescaline)
- Deumescaline
- α,α-Dideuterophenethylamine
References
[edit]- ^ a b c d e f g h i j k Trachsel D, Lehmann D, Enzensperger C (2013). Phenethylamine: von der Struktur zur Funktion [Phenethylamines: From Structure to Function]. Nachtschatten-Science (in German) (1 ed.). Solothurn: Nachtschatten-Verlag. pp. 677–705. ISBN 978-3-03788-700-4. OCLC 858805226. Archived from the original on 21 August 2025.
- ^ a b c d e f g h i Shulgin A, Shulgin A (September 1991). PiHKAL: A Chemical Love Story. Berkeley, California: Transform Press. ISBN 0-9630096-0-5. OCLC 25627628. "The 4-D and the β-D are two of five obvious deuterium isomer derivatives of mescaline. The three remaining are: (1) 3,5-D (4-methoxy-3,5-bis-trideuteromethoxyphenethylamine); (2) 2,6-D (2,6-dideutero-3,4,5-trimethoxyphenethylamine); and (3) α-D (α,α-dideutero-3,4,5-trimethoxyphenethylamine). I fully expect both 3,5-D and 2,6-D to be indistinguishable from mescaline in effect, since it is known that not much metabolism takes place in man at these locations of the molecule. The last compound, α-D, could be quite a different matter. The principal metabolite of mescaline is 3,4,5-trimethoxyphenylacetic acid, and this product requires enzymatic attack at the exact position where the deuteriums will be located. To the extent that they are harder to remove (come off more slowly or to a lesser degree), to that extent the molecule will be more potent in man, and the dosage required for effects will be less. The compound will be easily made by the reduction of 3,4,5-trimethoxyphenylacetonitrile with lithium aluminum deuteride. And if there is a believable difference between α-D and mescaline, it will be necessary to synthesize each of the two optically active α-mono-deutero analogs. That will be quite a challenge."
- ^ a b c d e f Jacob P, Shulgin AT (1994). "Structure-Activity Relationships of the Classic Hallucinogens and Their Analogs". In Lin GC, Glennon RA (eds.). Hallucinogens: An Update (PDF). National Institute on Drug Abuse Research Monograph Series. Vol. 146. National Institute on Drug Abuse. pp. 74–91. PMID 8742795. Archived from the original on 13 July 2025.
The two last compounds in table 1 are the only known deuterium analogs that have been explored in humans, and neither can be distinguished from mescaline. Other uniquely deuterated isotopomers that may be of interest are 3,5-(bis-trideuteromethoxy)-4-methoxyphenethylamine (3,5-D); 2,6-dideuteromescaline (2,6-D), and α,α-dideuteromescaline (α-D). The last compound, being deuterated at the most probable primary site for metabolic attack, might be of a different potency due to the kinetics of a-proton removal, and a study of the (R)-α-monodeuteroisotopomers [(R)-α-D] and (S)-α-monodeuteroisotopomers [(S)-α-D] might be informative. None of these latter compounds has as yet been studied.
- ^ a b c d e f Shulgin AT (2003). "Basic Pharmacology and Effects". In Laing RR (ed.). Hallucinogens: A Forensic Drug Handbook. Forensic Drug Handbook Series. Elsevier Science. pp. 67–137. ISBN 978-0-12-433951-4. Archived from the original on 13 July 2025.
Two of the five stable deuterated analogues of mescaline have also been studied in humans. The α,α-dideutero mescaline would be compromised by this conversion to the phenylacetic acid, but still could be valuable as a measure of the chiral position sensitivity of metabolism as the separate R and S isomers, but the β,β-dideutero analogue of mescaline has been made and evaluated. Also, the 4-trideuteromescaline (4-D) has been explored as a separate and new drug. The question asked here is whether any of these hydrogen atom positions represent reaction sites that might contribute to the understanding of the mechanism of action of mescaline. In both of these analogues, the observed psychopharmacological activity was in the 200-400mg range in humans, indistinguishable from mescaline itself. The three possible remaining deutero-analogues (the 3,5-dimethoxyl group hexadeuteromescaline, the ring 2,6-dideuteromescaline and the di-alpha-deuteromescaline) are unexplored.
- ^ Dinis-Oliveira RJ, Pereira CL, da Silva DD (2019). "Pharmacokinetic and Pharmacodynamic Aspects of Peyote and Mescaline: Clinical and Forensic Repercussions". Current Molecular Pharmacology. 12 (3): 184–194. doi:10.2174/1874467211666181010154139. PMC 6864602. PMID 30318013.
- ^ Mueller L, Klaiber A, Ley L, Becker AM, Thomann J, Luethi D, et al. (July 2025). "Pharmacokinetics, Pharmacodynamics, and Urinary Recovery of Oral Mescaline Hydrochloride in Healthy Participants". Clinical Pharmacokinetics. 64 (10): 1495–1506. doi:10.1007/s40262-025-01544-x. PMC 12479620. PMID 40658345.
- ^ "Controlled Drugs and Substances Act". Department of Justice Canada. Retrieved 19 January 2026.