C-(4,5,6-Trimethoxyindan-1-yl)methanamine: A Mescaline Analogue Designed Using a Homology Model of the 5-HT2AReceptor
Thomas H. Mclean, James J. Chambers, Jason C. Parrish, Michael R Braden, Danuta Marona‐lewicka, Deborah Kurrasch‐orbaugh, David E. Nichols
Journal of Medicinal Chemistry June 21, 2006 DOI: 10.1021/jm060272y (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Interventions | C-(4 5 6-trimethoxyindan-1-yl)-methanamine |
| Topics | Mescaline |
| Keywords | Potency Stereochemistry Homology modeling Enantiomer Receptor Pharmacology Biochemistry Hallucinogen In vitro Enzyme Alkaloids |
| Citations | 24 |
| Key findings | A conformationally restricted mescaline analogue showed three-fold higher affinity and potency at the 5-HT(2A) receptor and five-fold greater potency than mescaline in drug discrimination tests, with the R-(+) enantiomer being the active form. |
Abstract
A conformationally restricted analogue of mescaline, C-(4,5,6-trimethoxyindan-1-yl)-methanamine, was designed using a 5-HT(2A) receptor homology model. The compound possessed 3-fold higher affinity and potency than and efficacy equal to that of mescaline at the 5-HT(2A) receptor. The new analogue substituted fully for LSD in drug discrimination studies and was 5-fold more potent than mescaline. Resolution of this analogue into its enantiomers corroborated the docking experiments, showing the R-(+) isomer to have higher affinity and potency and to have efficacy similar to that of mescaline at the 5-HT(2A) receptor.