M. Hoener

2 papers in the library · 64 citations · publishing 2019

Papers

Cytochrome P450 enzymes contribute to the metabolism of LSD to nor-LSD and 2-oxo-3-hydroxy-LSD: Implications for clinical LSD use.

Biochemical Pharmacology June 1, 2019 D. Luethi, M. Hoener, S. Krähenbühl et al. 46 citations

LSD is metabolized in the human liver into two main metabolites, nor-LSD and O-H-LSD, but only in small amounts—less than 1% of the parent compound was converted over four hours in laboratory experiments using human liver microsomes. Several cytochrome P450 enzymes contribute to this metabolism: CYP2D6, 2E1, and 3A4 for nor-LSD, and CYP1A2, 2C9, 2E1, and 3A4 for O-H-LSD. Enzyme induction by rifampicin increased metabolite formation, while omeprazole had a minor effect on nor-LSD. LSD and nor-LSD both activate serotonin receptors (5-HT1A, 5-HT2A, 5-HT2B, 5-HT2C), with nor-LSD showing lower affinity at the 5-HT2C receptor. O-H-LSD had much weaker receptor activity, suggesting it is inactive. Genetic variations or drug interactions affecting these enzymes could alter LSD's effects.

DOI: 10.1016/j.bcp.2019.04.013 Medicine Chemistry

Monoamine receptor interaction profiles of 4-aryl-substituted 2,5-dimethoxyphenethylamines (2C-BI derivatives).

European Journal of Pharmacology July 1, 2019 D. Luethi, R. Widmer, D. Trachsel et al. 18 citations

Certain ring-substituted phenethylamines produce psychedelic effects mainly through serotonin 5-HT2A receptors. 2C-BI derivatives, a class of 4'-aryl substituted 2,5-dimethoxyphenethylamines, were tested for binding and activity at monoamine receptors and transporters. Several 2C-BI compounds bound strongly to human serotonergic and adrenergic receptors and to rat and mouse trace amine-associated receptor 1. 2C-BI-8 and 2C-BI-12 activated serotonin 5-HT2A and 5-HT2B receptors at submicromolar concentrations, while only 2C-BI-1 and 2C-BI-7 activated human trace amine-associated receptor 1. 2C-BI-3 and 2C-BI-4 interacted weakly with monoamine transporters. The high affinities at the 5-HT2A receptor suggest a sterically tolerant binding pocket, and potent partial activation by 2C-BI-8 and 2C-BI-12 indicates potential psychedelic effects similar to other 2C compounds.

DOI: 10.1016/j.ejphar.2019.05.014 Medicine Chemistry