12-Methoxy-LSD

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12-Methoxy-LSD
12-MeO-LSD structure.png
Clinical data
Other names12-MeO-LSD; "5-MeO-LSD"; "5-Methoxy-LSD"; 9,10-Didehydro-N,N-diethyl-6-methyl-12-methoxyergoline-8β- carboxamide.
Drug class Serotonin receptor modulator
Identifiers
  • (6aR,9R)-N,N-diethyl-1-methoxy-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide
CAS Number
PubChem CID
ChemSpider
CompTox Dashboard (EPA)
Chemical and physical data
Formula C21H27N3O2
Molar mass 353.466 g·mol−1
3D model (JSmol)
  • CCN(CC)C(=O)[C@H]1CN([C@@H]2CC3=CNC4=C3C(=C(C=C4)OC)C2=C1)C
  • InChI=1S/C21H27N3O2/c1-5-24(6-2)21(25)14-9-15-17(23(3)12-14)10-13-11-22-16-7-8-18(26-4)20(15)19(13)16/h7-9,11,14,17,22H,5-6,10,12H2,1-4H3/t14-,17-/m1/s1
  • Key:AYFDTTGGASATFS-RHSMWYFYSA-N

12-Methoxy-LSD is a drug of the ergoline and lysergamide families and a derivative of lysergic acid diethylamide (LSD). [1] [2] [3] [4] In terms of chemical structure, 12-methoxy-LSD is to LSD as 5-MeO-DMT is to dimethyltryptamine (DMT). [5]

Contents

It has been reported that 12-methoxy-LSD does not produce hallucinogenic effects in humans. [1] [2] [3] However, it is nonetheless pharmacologically active in animal studies. [1] The drug's effects in rabbits include antiserotonergic activity (20% of that of LSD) and hyperthermia (dose ratio relative to LD50 Tooltip median lethal dose of 1:17 for 12-methoxy-LSD and 1:725 for LSD). [1] In addition, like LSD, it is highly potent in terms of lethality, with a median lethal dose (LD50) of 0.1 mg/kg i.v. Tooltip intravenous administration in rabbits (relative to 0.1 mg/kg for LSD). [1] [3] [4] 12-Methoxy-LSD also produces LSD-like electroencephalogram (EEG) changes in rabbits. [6]

Presumably 12-methoxy-LSD acts as an agonist of serotonin and dopamine receptors, as with LSD and other related lysergamides, but its pharmacology has not been studied with modern techniques. [1] [3]

12-Methoxy-LSD was first described in the scientific literature by 1967. [1] Subsequently, it was further described in the 1970s and 1980s. [3] [4] [7] [6] [8] [2]

An analogue of 12-methoxy-LSD is 12-hydroxy-LSD, which would be structurally akin to bufotenin (5-HO-DMT). [1] [3] [8] As with 12-methoxy-LSD, it has been reported that 12-hydroxy-LSD is inactive as a psychedelic in humans. [1] Contrary to this report however, Michael Valentine Smith claimed in his 1981 book Psychedelic Chemistry that 12-hydroxy-LSD has "about the same activity as LSD". [8]

See also

References

  1. 1 2 3 4 5 6 7 8 9 M. Taeschler (1967). "Pharmacology of Psychotomimetic Agents". In Brill H, Cole JO, Deniker P, Hippius H, Bradley PB (eds.). Neuro-psycho-pharmacology: Proceedings of the Fifth International Congress of the Collegium Internationale Neuropsychopharmacologicum. Washington, D.C., 28-31 March 1966. International Congress Series. Vol. 129. Amsterdam: Excerpta Medica. pp. 393–397. ISSN   0531-5131. OCLC   458719. Fig. 2. Listed are several pharmacodynamic properties of various lysergic acid derivatives: Ps = psychotomimetic activity in man; P.I. = pyretogenic index (ratio of the i.v. LD50 and the dose producing an increase in rectal temperature of 1°C in rabbits); Tox. = i.v. LD50 in rabbits; 5-HT = antiserotonin activity in isolated rat uterus expressed in percentages of that for LSD-25. It is evident that the psychotomimetic action does not correlate with 5-HT antagonism nor with the toxicity of the compound. A close correlation is observed with the pyretogenic index (i.e. the specific pyretogenic action in rabbits. [...] LSD: 5-HT: 100. TOX.: 0,3. P.I.: 725. Ps.: +. [...] 12 CH3O-: 5-HT: 20. TOX.: 0,1. P.I.: 17. Ps.: –.
  2. 1 2 3 Donald A. Cooper (1989). "Future Synthetic Drugs of Abuse". Proceedings of the International Symposium on the Forensic Aspects of Controlled Substances: March 28-April 1, 1988, Forensic Science Research and Training Center, FBI Academy, Quantico, Virginia. Laboratory Division, Federal Bureau of Investigation, U.S. Department of Justice. pp. 79–103 (81). ISBN   978-0-932115-09-6 . Retrieved 18 March 2025. The assessment of a particular LSD derivative as a candidate for a future [Controlled Substance Analog (CsA)] involves the consideration of several points. The most important are those attempts made by other researchers to modify the structure of LSD while retaining hallucinogenic activity. To date, all attempts to modify the tetracyclic ring system have resulted in a loss of hallucinogenic activity. For instance, of the four possible C-8 stereoisomers only the dextro isomer of LSD is hallucinogenic (Rothlin 1957a). Modification of the amide alkyl substituents also reduces hallucinogenic activity substantially (Usdin and Efron 1972). Additionally, substitution with either a hydroxyl or a methoxy at the C-12 of LSD results in a compound with no hallucinogenic activity (Usdin and Efron 1972), whereas a comparably substituted methoxyindolealkylamine appears to always be hallucinogenic (Gessner and Page 1962). The only structural modification which results in the maintenance of hallucinogenic activity on par with LSD is the substitution of either a methyl or an acetyl to the indole nitrogen (Rothlin 1957b).
  3. 1 2 3 4 5 6 Usdin E, Efron DH (1972). Psychotropic Drugs and Related Compounds. National Institute of Mental Health. pp. 96, 100. ASIN   B002X3CDIY. 277. 12-METHOXY LYSERGIC ACID DIETHYLAMIDE. 9,10-Didehydro-N,N-diethyl-6-methyl-12-methoxy-ergoline-8β-carboxamide. [...] LD50: 0.1 mg./kg./i.v/R. (1460). Action: Not [hallucinogen (H)] (1460). [...] 1460. Taeschler, M. In: 'Neuropsychopharmacology.' Ed. by Brill, H., Cole, J.O., Deniker, P., Hippius, H., & Bradley, P.B. Amsterdam: Excerpta Medica Foundation (1967), pp. 393-397.
  4. 1 2 3 D. V. Siva Sankar (1975). "Molecular Investigations: Relations Between Molecular Structure and Psychobiological Activity / Molecular Aspects: Structure-Activity Relations". LSD - A Total Study (PDF). Westbury, N.Y.: PJD Publications. pp. 65–106 (77, 82, 95). ISBN   978-0-9600290-3-7. LCCN   72-95447. STRUCTURAL DETAILS OF SOME LYSERGATES [...] 12-Methoxy-LSD [...] TABLE I [...] COMPOUND: 12-Methoxy lysergic acid diethylamide. Chemical Name: 12-Didehydro-N,N-diethyl-6- methoxy-ergoline-8β-carboxamide. LD50: 0.1 mg/kg/iv/R. [...] Abbreviations used: m for mouse, r for rat and R for rabbit. [...] TABLE II Structure and Biological Activities of Lysergates [...] Compound No.: 11. R1: C2H5. R2: C2H5. R3: H. R4: H. R5: OCH3. R6: H. R7: CH3. Hallucinogenic Activity: ?. Pyretogenic Effect: ?. Anti-HT: ?. Excitation Syndrome: ?. Toxicity: ?.
  5. ↑ "Ergoline-8-beta-carboxamide, 9,10-didehydro-N,N-diethyl-12-methoxy-6-methyl-". PubChem. Retrieved 18 March 2025.
  6. 1 2 Siddik ZH, Barnes RD, Dring LG, Smith RL, Williams RT (October 1979). "The fate of lysergic acid DI[14C]ethylamide ([14C]LSD) in the rat, guinea pig and rhesus monkey and of [14C]iso-LSD in rat". Biochem Pharmacol. 28 (20): 3093–3101. doi:10.1016/0006-2952(79)90618-x. PMID   117811. EEG studies. Synthetic and biosynthetic metabolites of LSD were injected intravenously into conscious restrained male chinchilla rabbits. With LSD itself, de-ethyl-LSD, 12-hydroxy-LSD, 12-methoxy-LSD, 13-hydroxy-LSD, 13-methoxy-LSD and 13-hydroxy-LSD glucuronide, a persistent alerting EEG trace was seen as indicated by an increase in frequency and decrease in amplitude of the waveform. No changes were observed after administration of lysergic acid, di-LSD-disulphide [10], nor-LSD, 14-hydroxy-LSD-glucuronide, 14-methoxy-LSD, lumi-LSD or the metabolic 2-oxo-LSD.
  7. ↑ Mangner TJ, University M (1978). Potential Psychotomimetic Antagonists. N,n -diethyl-1-methyl-3-aryl-1, 2, 5, 6-tetrahydropyridine-5-carboxamides (Thesis). doi:10.7302/11268.
  8. 1 2 3 Smith M (1981). "[Chapter 7:] LSD". Psychedelic Chemistry. Loompanics Unlimited. pp. 103–137 (136). ISBN   978-0-915179-10-7 . Retrieved 18 March 2025. 2,3-dihydro-LSD can be converted directly to 12-hydroxy-LSD, which has about the same activity as LSD and this process is also given below.


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