Comparison of solution conformational preferences for the hallucinogens bufotenin and psilocin using 360-MHz proton NMR spectroscopy.
G P Migliaccio, T L Shieh, S R Byrn, B A Hathaway, D E Nichols
Journal of Medicinal Chemistry February 1, 1981 DOI: 10.1021/jm00134a016 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Topics | Psilocybin |
| Citations | 34 |
| Key findings | The difference in biological activity between bufotenin and psilocin is largely due to a difference in basicity, with pKa values of 8.47 for psilocin and 9.67 for bufotenin. |
Abstract
The 360-MHz 1H NMR spectra of bufotenin and psilocin were obtained, both as the free bases in CDCl3 and as protonated salts in D2O. Coupling constants for the side-chain methylenes were derived using the LAOCN3 program. These time-averaged coupling constants indicate that the trans and gauche rotamers of both compounds have about equal energy in D2O. There is a slight excess of the trans rotamer of bufotenin in CDCl3. For psilocin, in contrast, the gauche form is highly favored in CDCl3. The magnitude of this stabilization was estimated at about 1 kcal/mol using rotamer populations and free energy of transfer from published partitioning studies. It is suggested that this could result from a very weak hydrogen bond. On the other hand, the difference in partitioning between bufotenin and psilocin, which seems to be a major determinant of biological activity, is largely due to a difference in the basicity of the two compounds. The pKa values for the amino group of psilocin and bufotenin were determined to be 8.47 and 9.67, respectively.
Comparable studies
Other experimental studies on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Healthy human volunteers | 1998 | Experimental study | |
| Validation of the revised Mystical Experience Questionnaire in experimental sessions with psilocybin Participants in controlled laboratory experiments receiving a moderate to high oral... | 2015 | Validation study using pooled data from five laboratory experiments | n = 184 |
| Broadband Cortical Desynchronization Underlies the Human Psychedelic State Healthy human participants | 2013 | Experimental study | |
| Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer Participants with cancer-related psychiatric distress who completed a parent randomized... | 2020 | Long-term within-subjects follow-up analysis | n = 15 |
| Enzymatic Synthesis of Psilocybin | 2017 | Laboratory study |
Citations in the library
Cited by 25
- The neural basis of psychedelic action. Nature Neuroscience October 24, 2022
- Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions. Current Drug Metabolism October 1, 2010
- Bufo toads and bufotenine: fact and fiction surrounding an alleged psychedelic. Journal of Psychoactive Drugs 1996
- Synthesis and Biological Evaluation of Tryptamines Found in Hallucinogenic Mushrooms: Norbaeocystin, Baeocystin, Norpsilocin, and Aeruginascin Journal of Natural Products February 20, 2020
- Bufotenine: toward an understanding of possible psychoactive mechanisms. Journal of Psychoactive Drugs 2000
and 20 more in the library