Document Detail

Design, synthesis, and biological evaluation of aminoalkylindole derivatives as cannabinoid receptor ligands with potential for treatment of alcohol abuse.
MedLine Citation:
PMID:  23631463     Owner:  NLM     Status:  MEDLINE    
Attenuation of increased endocannabinoid signaling with a CB1R neutral antagonist might offer a new therapeutic direction for treatment of alcohol abuse. We have recently reported that a monohydroxylated metabolite of the synthetic aminoalkylindole cannabinoid JHW-073 (3) exhibits neutral antagonist activity at CB1Rs and thus may serve as a promising lead for the development of novel alcohol abuse therapies. In the current study, we show that systematic modification of an aminoalkylindole scaffold identified two new compounds with dual CB1R antagonist/CB2R agonist activity. Similar to the CB1R antagonist/inverse agonist rimonabant, analogues 27 and 30 decrease oral alcohol self-administration without affecting total fluid intake and block the development of alcohol-conditioned place preference. Collectively, these initial findings suggest that design and systematic modification of aminoalkylindoles such as 3 may lead to development of novel cannabinoid ligands with dual CB1R antagonist/CB2R agonist activity with potential for use as treatments of alcohol abuse.
Tamara Vasiljevik; Lirit N Franks; Benjamin M Ford; Justin T Douglas; Paul L Prather; William E Fantegrossi; Thomas E Prisinzano
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-05-22
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  56     ISSN:  1520-4804     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-06-13     Completed Date:  2013-08-20     Revised Date:  2014-06-16    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4537-50     Citation Subset:  IM    
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MeSH Terms
Alcoholism / drug therapy*
CHO Cells
Cannabinoid Receptor Agonists / chemical synthesis*,  chemistry,  pharmacology
Cannabinoid Receptor Antagonists / chemical synthesis*,  chemistry,  pharmacology
Conditioning, Classical / drug effects
Drug Design
Drug Inverse Agonism
Ethanol / administration & dosage,  pharmacology
Indoles / chemical synthesis*,  chemistry,  pharmacology
Receptor, Cannabinoid, CB1 / antagonists & inhibitors
Receptor, Cannabinoid, CB2 / agonists
Receptors, Cannabinoid / metabolism*
Self Administration
Structure-Activity Relationship
Grant Support
Reg. No./Substance:
0/Cannabinoid Receptor Agonists; 0/Cannabinoid Receptor Antagonists; 0/Indoles; 0/Ligands; 0/Receptor, Cannabinoid, CB1; 0/Receptor, Cannabinoid, CB2; 0/Receptors, Cannabinoid; 3K9958V90M/Ethanol

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

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