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    
Abstract/OtherAbstract:
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.
Authors:
Tamara Vasiljevik; Lirit N Franks; Benjamin M Ford; Justin T Douglas; Paul L Prather; William E Fantegrossi; Thomas E Prisinzano
Related Documents :
23627993 - Relationship between participation in leisure activities and constraints on taiwanese b...
18974673 - Subject and interviewer determinants of the adequacy of the dynamic interview.
2930413 - Modifiability of trait anxiety and neuroticism: a meta-analysis of the literature.
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    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Alcoholism / drug therapy*
Animals
CHO Cells
Cannabinoid Receptor Agonists / chemical synthesis*,  chemistry,  pharmacology
Cannabinoid Receptor Antagonists / chemical synthesis*,  chemistry,  pharmacology
Conditioning, Classical / drug effects
Cricetinae
Cricetulus
Drug Design
Drug Inverse Agonism
Ethanol / administration & dosage,  pharmacology
Humans
Indoles / chemical synthesis*,  chemistry,  pharmacology
Ligands
Mice
Receptor, Cannabinoid, CB1 / antagonists & inhibitors
Receptor, Cannabinoid, CB2 / agonists
Receptors, Cannabinoid / metabolism*
Self Administration
Structure-Activity Relationship
Grant Support
ID/Acronym/Agency:
DA018151/DA/NIDA NIH HHS; R01 DA018151/DA/NIDA NIH HHS
Chemical
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
Comments/Corrections

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


Previous Document:  Interconception Care for Women With Prior Gestational Diabetes Mellitus.
Next Document:  Cardiac metastasis from yolk sac tumor: case report and review.