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, M. Braden, Danuta Marona‐lewicka, Deborah Kurrasch‐orbaugh, David E. Nichols
Journal of Medicinal Chemistry June 21, 2006 DOI: 10.1021/jm060272y via OpenAlex
Summary
AI-generated from the abstractA new molecule, C-(4,5,6-trimethoxyindan-1-yl)-methanamine, was designed based on a computer model of the 5-HT(2A) receptor. This compound showed three times higher affinity and potency than mescaline at the receptor, with equal efficacy. In drug discrimination tests, it fully substituted for LSD and was five times more potent than mescaline. Separating the molecule into its mirror-image forms confirmed the computer predictions: the R-(+) isomer had higher affinity and potency than the S-(-) isomer, with efficacy similar to mescaline at the 5-HT(2A) receptor.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Topics | Mescaline |
| Keywords | Potency Stereochemistry Homology modeling Enantiomer |
| Citations | 24 |
| Key finding | 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.