Correlating the Metabolic Stability of Psychedelic 5-HT2A Agonists with Anecdotal Reports of Human Oral Bioavailability

Research output: Contribution to journalJournal articleResearchpeer-review

Sebastian Leth-Petersen, Christoffer Bundgaard, Martin Hansen, Martin A Carnerup, Jan Kehler, Jesper Langgaard Kristensen

2,5-Dimethoxyphenethylamines and their N-benzylated derivatives are potent 5-HT2A agonists with psychedelic effects in humans. The N-benzylated derivatives are among the most selective 5-HT2A agonists currently available and their usage as biochemical and brain imaging tools is increasing, yet very little is known about the relationships between the structure of the ligands and their pharmacokinetic profile. In order to evaluate the potential of these compounds for in vivo applications we have determined the microsomal stability of 11 phenethylamines and 27 N-benzylated derivatives thereof using human liver microsomes. We found that the N-benzylated phenethylamines have much higher intrinsic clearance than the parent phenethylamines. We hypothesize that their low hepatic stability renders them orally inactive due to first pass metabolism, which is supported by anecdotal data from recreational use of these compounds.
Original languageEnglish
JournalNeurochemical Research
Volume39
Issue number10
Pages (from-to)2018-2023
Number of pages6
ISSN0364-3190
DOIs
Publication statusPublished - 12 Feb 2014

ID: 103038247