C-(4,5,6-trimethoxyindan-1-yl)methanamine: a mescaline analogue designed using a homology model of the 5-HT2A receptor

  • J Med Chem. 2006 Jul 13;49(14):4269-74. doi: 10.1021/jm060272y.
Thomas H McLean  1 ,  James J Chambers ,  Jason C Parrish ,  Michael R Braden ,  Danuta Marona-Lewicka ,  Deborah Kurrasch-Orbaugh ,  David E Nichols
Affiliations
  • 1. Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Purdue University, West Lafayette, Indiana 47907-1333, USA.
PMID: 16821786 DOI: 10.1021/jm060272y
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.

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