Lysergol

Lysergol
Clinical data
Other namesLOL; 9,10-Didehydro-6-methyl-8β-hydroxymethylergoline; 6-Methyl-9,10-didehydroergolin-8β-yl)methanol
Drug classSerotonin receptor modulator; Serotonin 5-HT2A receptor agonist
ATC code
  • None
Identifiers
  • [(6aR,9R)-7-methyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinolin-9-yl]methanol
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.009.113 Edit this at Wikidata
Chemical and physical data
FormulaC16H18N2O
Molar mass254.333 g·mol−1
3D model (JSmol)
  • OC[C@@H]3/C=C2/c4cccc1c4c(c[nH]1)C[C@H]2N(C3)C
  • InChI=1S/C16H18N2O/c1-18-8-10(9-19)5-13-12-3-2-4-14-16(12)11(7-17-14)6-15(13)18/h2-5,7,10,15,17,19H,6,8-9H2,1H3/t10-,15-/m1/s1 checkY
  • Key:BIXJFIJYBLJTMK-MEBBXXQBSA-N checkY
 X markNcheckY (what is this?)  (verify)

Lysergol, also known as LOL (from Lysergol) or as 9,10-didehydro-6-methyl-8β-hydroxymethylergoline, is an alkaloid of the ergoline family that occurs as a minor constituent in some species of fungi (most within Claviceps), and in the morning glory family of flowering plants, including the hallucinogenic seeds of Rivea corymbosa (ololiuhqui), Argyreia nervosa (Hawaiian baby woodrose), and Ipomoea violacea.

Use and effects

In contrast to LSD and other lysergamides, lysergol is non-hallucinogenic in humans and is described as not contributing to the hallucinogenic effects of morning glory seeds. It was inactive as a psychedelic drug at doses of 2 to 8 mg orally, up to more than 100 times the effective dose of LSD, but did produce light sedative-like effects at the 8 mg dose.

Pharmacology

Pharmacodynamics

The binding of lysergol, as well as of isolysergol, to the serotonin 5-HT1A, 5-HT2A, 5-HT2B, and 5-HT2C receptors has been described. It is an agonist of the serotonin 5-HT2A receptor and α1-adrenergic receptor.

Chemistry

Synthesis

Lysergol can be synthesised using a tandem reaction to construct the piperidine skeleton and a rhodium-catalyzed [3 + 2] annulation in the late-stage indole formation.

Analogues

Analogues of lysergol include lysergine, lysergic acid, and descarboxylysergic acid, among others.

Society and culture

Lysergol is not a controlled substance in the United States. Its possession and sale is also legal under the U.S. Federal Analog Act because it does not have a known pharmacological action or a precursor relationship to LSD, which is a controlled substance. However, lysergol is an intermediate in the manufacture of some ergoloid medicines (e.g., nicergoline).

See also

References

  1. 1 2 Fanchamps A (1978). "Some Compounds With Hallucinogenic Activity". In Berde B, Schild HO (eds.). Ergot Alkaloids and Related Compounds. Handbook of Experimental Pharmacology (HEP). Vol. 49. Berlin, Heidelberg: Springer Berlin Heidelberg. pp. 567–614. doi:10.1007/978-3-642-66775-6_8. ISBN 978-3-642-66777-0. Lysergol (No. 79a) has no effect up to 6 mg, but 8 mg produce a slight sedation (HELM et al., 1968). [...] Table 2. Psychotomimetic activity and some pharmacodynamic effects of structural analogues of LSD [...]
  2. ↑ Brimblecombe RW, Pinder RM (1975). "Indolealkylamines and Related Compounds". Hallucinogenic Agents. Bristol: Wright-Scientechnica. pp. 98–144. ISBN 978-0-85608-011-1. OCLC 2176880. OL 4850660M. d-Lysergic acid amide (ergine) is the major constituent of the seeds of both Rivea corymbosa and Ipomoea violacea, together with smaller amounts of d-isolysergic acid amide (isoergine), chanoclavine, elymoclavine, and the N-(1-hydroxyethyl)amides of lysergic and isolysergic acids. [...] It is clear that the pharmacologically active constituents of ololiuqui are the isomeric lysergic acid amides. [...] Heim and his colleagues suggest that the overall effects of ololiuqui are due to these two compounds, the d-lysergic acid amide giving intoxication with strong autonomic side-effects and the d-isolysergic acid amide producing some euphoria, synaesthesia, and altered time experience. Certainly elymoclavine, lysergol, chanoclavine, and ergometrine produce no psychic changes in man (Isbell and Gorodetzky, 1966; Hofmann, 1968), though the first two do produce central excitation in animals (Yui and Takeo, 1958).
  3. 1 2 Heim E, Heimann H, Lukács G (1968). "Die psychische Wirkung der mexikanischen Droge "Ololiuqui" am Menschen" [Psychotomimetic effects of the mexican drug “Ololiuqui”]. Psychopharmacologia (in German). 13 (1): 35–48. doi:10.1007/BF00401617. ISSN 0033-3158.
  4. ↑ WO 2023018480, Wipf PU, Tasker NR, Pazur EJ, "Selective psychedelic compounds", published 21 June 2022, assigned to Univ Pittsburgh Commonwealth Sys Higher Education [Us] and University of Pittsburgh - Of the Commonwealth System of Higher Education
  5. ↑ Tasker NR, Wipf P (October 2022). "A Short Synthesis of Ergot Alkaloids and Evaluation of the 5-HT1/2 Receptor Selectivity of Lysergols and Isolysergols". Organic Letters. 24 (40): 7255–7259. doi:10.1021/acs.orglett.2c02569. PMID 35993579.
  6. ↑ Pertz H (October 1996). "Naturally occurring clavines: antagonism/partial agonism at 5-HT2A receptors and antagonism at alpha 1-adrenoceptors in blood vessels". Planta Medica. 62 (5): 387–392. doi:10.1055/s-2006-957922. PMID 8923801.
  7. ↑ Yuan H, Guo Z, Luo T (February 2017). "Synthesis of (+)-Lysergol and Its Analogues To Assess Serotonin Receptor Activity". Organic Letters. 19 (3): 624–627. doi:10.1021/acs.orglett.6b03779. PMID 28106398.

Further reading