Synthesis and evaluation of 2,3-dihydrobenzofuran analogs of the hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane: drug discrimination studies in rats

Two analogues, 6-(2-aminopropyl)-5-methoxy-2,3-dihydrobenzofuran and 6-(2-aminopropyl)-5-methoxy-2-methyl-2,3-dihydrobenzofuran, of the hallucinogenic agent 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) were synthesized and tested in the two-lever drug discrimination paradigm. In rats traine...

Full description

Saved in:
Bibliographic Details
Published in:Journal of medicinal chemistry 1986-02, Vol.29 (2), p.302-304
Main Authors: Nichols, David E, Hoffman, Andrew J, Oberlender, Robert A, Riggs, Robert M
Format: Article
Language:English
Subjects:
Amphetamines - pharmacology
Animals
Benzofurans - chemical synthesis
Benzofurans - pharmacology
Chemistry
Discrimination Learning - drug effects
DOM 2,5-Dimethoxy-4-Methylamphetamine - analogs & derivatives
DOM 2,5-Dimethoxy-4-Methylamphetamine - pharmacology
Exact sciences and technology
Hallucinogens - chemical synthesis
Hallucinogens - pharmacology
Heterocyclic compounds
Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives
Lysergic Acid Diethylamide - pharmacology
Male
Molecular Conformation
Organic chemistry
Preparations and properties
Rats
Rats, Inbred Strains
Structure-Activity Relationship
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Two analogues, 6-(2-aminopropyl)-5-methoxy-2,3-dihydrobenzofuran and 6-(2-aminopropyl)-5-methoxy-2-methyl-2,3-dihydrobenzofuran, of the hallucinogenic agent 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) were synthesized and tested in the two-lever drug discrimination paradigm. In rats trained to discriminate saline from LSD tartrate (0.08 mg/kg), stimulus generalization occurred to both of the 2,3-dihydrobenzofuran analogues but at doses more than 10-fold higher than for DOM. A possible explanation for this dramatic attenuation of LSD-like activity could involve a highly directional electrophilic binding site on the receptor that cannot accept the orientation of the unshared electron pairs on the heterocyclic oxygen atom in the benzofurans.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00152a022