Document Detail


Synthesis and LSD-like discriminative stimulus properties in a series of N(6)-alkyl norlysergic acid N,N-diethylamide derivatives.
MedLine Citation:
PMID:  4032428     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A convenient method for the synthesis of N(6)-alkyl norlysergic acid N,N-diethylamide derivatives was developed. A series of these compounds was synthesized and tested for substitution in the two-lever drug discrimination assay, in rats trained to discriminate injections of d-LSD tartrate (185.5 nmol/kg, ip) from saline. A dose-response curve for each of the compounds in the series was generated. Structure-activity relationships were developed, based on comparison of the estimated ED50 values from these curves. Of the compounds that substituted for LSD, the N(6)-ethyl and -allyl were approximately 2-3 times more potent than LSD itself. The N(6)-propyl was equipotent to LSD, while the isopropyl derivative was half as active. The n-butyl compound was 1 order of magnitude less potent than LSD, suggesting a similarity to the SAR of certain serotonin and dopamine agonists. By contrast, no generalization occurred to norlysergic acid N,N-diethylamide and the N(6)-2-phenethyl derivative.
Authors:
A J Hoffman; D E Nichols
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  28     ISSN:  0022-2623     ISO Abbreviation:  J. Med. Chem.     Publication Date:  1985 Sep 
Date Detail:
Created Date:  1985-10-17     Completed Date:  1985-10-17     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1252-5     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Chemical Phenomena
Chemistry
Discrimination Learning / drug effects*
Lysergic Acid Diethylamide / analogs & derivatives*,  chemical synthesis,  pharmacology
Male
Rats
Structure-Activity Relationship
Grant Support
ID/Acronym/Agency:
2-S07-RR05586-15/RR/NCRR NIH HHS; DA-02189/DA/NIDA NIH HHS; RR01077/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
50-37-3/Lysergic Acid Diethylamide

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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