| Structural analogs of pyrazole and sulfonamide cannabinoids: effects on acute food intake in mice. | |
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MedLine Citation:
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PMID: 22975289 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Jenny L Wiley; Julie A Marusich; Yanan Zhang; Alan Fulp; Rangan Maitra; Brian F Thomas; Anu Mahadevan |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2012-09-06 |
Journal Detail:
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Title: European journal of pharmacology Volume: 695 ISSN: 1879-0712 ISO Abbreviation: Eur. J. Pharmacol. Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-10-16 Completed Date: 2013-03-19 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 62-70 Citation Subset: IM |
Copyright Information:
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Copyright © 2012 Elsevier B.V. All rights reserved. |
Affiliation:
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Research Triangle Institute, 3040 Cornwallis Drive, Research Triangle Park, NC 27709-2194, U.S.A. jwiley@rti.org |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals 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 Tetrahydrocannabinol / analogs & derivatives*, chemistry, metabolism, pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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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 |
| Chemical | |
Reg. No./Substance:
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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; 1972-08-3/Tetrahydrocannabinol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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