Receptor interaction profiles of 4-alkoxy-2,6-dimethoxyphenethylamines (Ψ derivatives) and related amphetamines
The Ψ derivatives mainly interacted with the 5-HT<sub>2A</sub> receptor, the primary target for psychedelics, as well as with the 5-HT<sub>2C</sub> receptor. The same 4-alkyloxy modification pattern on the related 2,4,5-trisubstituted derivatives exhibited generally slightly more potent 5-HT<sub>2A</sub> receptor binding and activation, whereas 3,4,5-trisubstituted derivatives interacted with lower potency; in humans, 2,4,6-trisubstituted derivatives may thus be less potent compared to their 2,4,5-trisubsititued counterparts but more potent compared to their 3,4,5-trisubsititued counterparts.
Authors
- Dino Luethi (ORCID: https://orcid.org/0000-0003-0874-4875)
- Marius C. Hoener (ORCID: https://orcid.org/0000-0001-6510-6250)
- Karolina E. Kolaczynska (ORCID: https://orcid.org/0000-0003-1714-0758)
- Matthias E. Liechti (ORCID: https://orcid.org/0000-0002-1765-9659)
- Daniel Trachsel
Institutions
- Roche (Switzerland) (CH)
- University of Basel (CH)
- University Hospital of Basel (CH)
- Universitätsklinik für Diabetologie, Endokrinologie, Ernährungsmedizin & Metabolismus (CH)
Publication Details
- Journal
- Frontiers in Pharmacology
- Published
- 2025-11-20
- DOI
- https://doi.org/10.3389/fphar.2025.1703480
- Primary Topic
- Psychedelics and Drug Studies
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Bundesamt für Gesundheit