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 Serotonin |
| 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.
Comparable studies
Other experimental studies on mescaline, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Enzymatic Formation of Psychotomimetic Metabolites from Normally Occurring Compounds Rabbit lung | 1961 | Experimental study | |
| PSYCHOTOMIMETICS, CLINICAL AND THEORETICAL CONSIDERATIONS: HARMINE, WIN-2299 AND NALLINE Schizophrenic patients | 1957 | Experimental study | |
| Phencyclidine, Lysergic Acid Diethylamide, and Mescaline: Cerebral Artery Spasms and Hallucinogenic Activity Isolated basilar and middle cerebral arteries | 1981 | Experimental study | |
| Acquired and Crossed Tolerance to Mescaline, LSD-25, and BOL-148 | 1959 | Experimental study | |
| Effects of Hallucinogenic and Tranquilizing Drugs on Serotonin Evoked Uterine Contractions. Uterus of spayed rat | 1956 | Experimental study |
Citations in the library
Cited by 12
- Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. Neuropharmacology May 1, 2020
- 1-Aminomethylbenzocycloalkanes: conformationally restricted hallucinogenic phenethylamine analogues as functionally selective 5-HT2A receptor agonists. Journal of Medicinal Chemistry September 21, 2006
- Dark Classics in Chemical Neuroscience: Mescaline ACS Chemical Neuroscience May 30, 2018
- Structure–activity relationships of serotonin 5‐HT2Aagonists Wiley Interdisciplinary Reviews Membrane Transport and Signalling February 28, 2012
- 5-HT2A receptors: Pharmacology and functional selectivity. Pharmacological Reviews April 23, 2025
and 7 more in the library
Cites 8
- Mapping the binding site pocket of the serotonin 5-Hydroxytryptamine2A receptor. Ser3.36(159) provides a second interaction site for the protonated amine of serotonin but not of lysergic acid diethylamide or bufotenin. Journal of Biological Chemistry June 21, 1996
- Enantiospecific Synthesis and Pharmacological Evaluation of a Series of Super-Potent, Conformationally Restricted 5-HT2A/2C Receptor Agonists Journal of Medicinal Chemistry January 26, 2001
- Dihydrobenzofuran Analogues of Hallucinogens. 4. Mescaline Derivatives Journal of Medicinal Chemistry September 1, 1997
- A Novel (Benzodifuranyl)aminoalkane with Extremely Potent Activity at the 5-HT2A Receptor Journal of Medicinal Chemistry December 1, 1998
- Synthesis and Pharmacological Characterization of a Series of Geometrically Constrained 5-HT2A/2C Receptor Ligands Journal of Medicinal Chemistry July 1, 2003
and 3 more in the library