C-(4,5,6-Trimethoxyindan-1-yl)methanamine: A Mescaline Analogue Designed Using a Homology Model of the 5-HT2AReceptor
Journal of Medicinal Chemistry – June 21, 2006
Source: OpenAlex
Summary
A novel analogue of mescaline demonstrated remarkable potency, exhibiting three times higher affinity at the 5-HT2A receptor compared to mescaline itself. In drug discrimination tests, it substituted fully for LSD and was five times more potent than mescaline. Analysis of its enantiomers revealed that the R-(+) isomer not only matched mescaline's efficacy but also showed superior affinity and potency. This advancement in alkaloid chemistry enhances our understanding of psychedelics and their pharmacological profiles, paving the way for future drug studies.
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.