Document Detail


Structural analogs of pyrazole and sulfonamide cannabinoids: effects on acute food intake in mice.
MedLine Citation:
PMID:  22975289     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Obesity contributes to a multitude of serious health problems. Given the demonstrated role of the endogenous cannabinoid system in appetite regulation, the purpose of the present study was to evaluate structural analogs of two cannabinoids, rimonabant (cannabinoid CB(1) receptor antagonist) and O-2050 (sulfonamide analog of Δ(8)-tetrahydrocannabinol), that showed appetite suppressant effects in previous studies. Structure-activity relationships of these two lead compounds were examined in several assays, including cannabinoid CB(1) and CB(2) receptor binding, food intake, and an in vivo test battery (locomotor activity, antinociception, ring immobility, and body temperature) in mice. Rimonabant and O-2050 reliably decreased feeding in mice; however, their analogs decreased feeding only at higher doses, even though some compounds had quite good cannabinoid CB(1) binding affinity. Results of the in vivo test battery were inconsistent, with some of the compounds producing effects characteristic of cannabinoid agonists while other compounds were inactive or were antagonists against an active dose of Δ(9)-tetrahydrocannabinol. These results demonstrate that reduction of food intake is not a characteristic effect of pyrazole and sulfonamide cannabinoid analogs with favorable cannabinoid CB(1) binding affinity, suggesting that development of these classes of cannabinoids for the treatment of obesity will require evaluation of their effects in a broad spectrum of pharmacological assays.
Authors:
Jenny L Wiley; Julie A Marusich; Yanan Zhang; Alan Fulp; Rangan Maitra; Brian F Thomas; Anu Mahadevan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-09-06
Journal Detail:
Title:  European journal of pharmacology     Volume:  695     ISSN:  1879-0712     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-16     Completed Date:  2013-03-19     Revised Date:  2013-12-04    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  62-70     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier B.V. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Dronabinol / analogs & derivatives*,  chemistry,  metabolism,  pharmacology
Eating / drug effects*
Male
Mice
Mice, Inbred ICR
Piperidines / chemistry*,  metabolism,  pharmacology*
Pyrans / chemistry*,  metabolism,  pharmacology*
Pyrazoles / chemistry*,  metabolism,  pharmacology*
Receptor, Cannabinoid, CB1 / metabolism
Receptor, Cannabinoid, CB2 / metabolism
Grant Support
ID/Acronym/Agency:
AA-017514/AA/NIAAA NIH HHS; AA-019740/AA/NIAAA NIH HHS; DA-005488/DA/NIDA NIH HHS; DA-03672/DA/NIDA NIH HHS; DA-09789/DA/NIDA NIH HHS; P01 DA009789/DA/NIDA NIH HHS; R01 DA003672/DA/NIDA NIH HHS; R01 DA005488/DA/NIDA NIH HHS; R03 AA017514/AA/NIAAA NIH HHS; R03 DA026593/DA/NIDA NIH HHS; R21 AA019740/AA/NIAAA NIH HHS; R21 DA026582/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
0/(6aR,10aR)-3-(1-methansulfonylamino-4-hexyn-6-yl)6a,7,10,10a-tetrahydro-6,6,9-trimethyl-6H-dibenzo(b,d)pyran; 0/Piperidines; 0/Pyrans; 0/Pyrazoles; 0/Receptor, Cannabinoid, CB1; 0/Receptor, Cannabinoid, CB2; 158681-13-1/rimonabant; 7J8897W37S/Dronabinol
Comments/Corrections

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