C-(4,5,6-trimethoxyindan-1-yl)methanamine: a mescaline analogue designed using a homology model of the 5-HT2A receptor.
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.
McLean
Thomas H
TH
Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Purdue University, West Lafayette, Indiana 47907-1333, USA.
Chambers
James J
JJ
Parrish
Jason C
JC
Braden
Michael R
MR
Marona-Lewicka
Danuta
D
Kurrasch-Orbaugh
Deborah
D
Nichols
David E
DE
D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D004193:Discrimination Learning / Q000187:drug effects; D006213:Hallucinogens / Q000138:chemical synthesis* / Q000494:pharmacology; D007189:Indans / Q000138:chemical synthesis* / Q000494:pharmacology; D007295:Inositol Phosphates / Q000096:biosynthesis; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D008635:Mescaline / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D008744:Methylamines / Q000138:chemical synthesis* / Q000494:pharmacology; D008958:Models, Molecular; D011869:Radioligand Assay; D051381:Rats; D044402:Receptor, Serotonin, 5-HT2A / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D058826:Serotonin 5-HT2 Receptor Agonists; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
C513158:C-(4,5,6-trimethoxyindan-1-yl)methanamine; D006213:Hallucinogens; D007189:Indans; D007295:Inositol Phosphates; D008744:Methylamines; D044402:Receptor, Serotonin, 5-HT2A; D058826:Serotonin 5-HT2 Receptor Agonists; D008238:Lysergic Acid Diethylamide; D008635:Mescaline