| Ajulemic acid (CT3): a potent analog of the acid metabolites of THC. | |
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MedLine Citation:
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PMID: 10903396 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The acid metabolites of THC were discovered almost 30 years ago and were later shown to posses modest analgesic and anti-inflammatory activity in a variety of models. Ajulemic acid (CT3) is a more potent analog of THC-11-oic acid in which a dimethylheptyl side chain is substituted for the pentyl side chain of the naturally occurring metabolite. It produces analgesia in the mouse hot plate, the PPQ writhing, the formalin and the tail clip assays. In the latter, it was equipotent to morphine; however, it showed a much greater duration of action. In the paw edema, subcutaneous air pouch and rat adjuvant-induced arthritis models of inflammation; it showed significant therapeutic activity at a dose of 0.2 mg/kg p.o. In the arthritis model it greatly reduced permanent damage to joints when compared to an indomethacin control as evidenced by an improved joint score over vehicle controls and by histopathological examination. In contrast to the NSAIDs, it was totally nonulcerogenic at therapeutically relevant doses. Moreover, it does not depress respiration, exhibit dependence, induce body weight loss or cause mutagenesis. It shows none of the typical actions in models of the psychotropic actions of cannabinoids suggesting that a good separation of desirable from undesirable effects was achieved. Studies on its mechanism of action are currently underway. The data thus far suggest the existence of a novel receptor for ajulemic acid with possible downstream effects on eicosanoid production, cytokine synthesis and metalloprotease activity. There is also circumstantial evidence for a putative endogenous ajulemic acid, namely, arachidonylglycine. |
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Authors:
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S H Burstein |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S.; Review |
Journal Detail:
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Title: Current pharmaceutical design Volume: 6 ISSN: 1381-6128 ISO Abbreviation: Curr. Pharm. Des. Publication Date: 2000 Sep |
Date Detail:
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Created Date: 2000-09-25 Completed Date: 2000-09-25 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 9602487 Medline TA: Curr Pharm Des Country: NETHERLANDS |
Other Details:
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Languages: eng Pagination: 1339-45 Citation Subset: IM |
Affiliation:
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Department of Biochemistry and Molecular Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA. sumner.burstein@umassmed.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Analgesics
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chemistry,
pharmacology Animals Cannabis / chemistry* Drug Design Humans Mice Rats Tetrahydrocannabinol / analogs & derivatives*, chemistry, pharmacology, toxicity |
| Grant Support | |
ID/Acronym/Agency:
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DA09017/DA/NIDA NIH HHS; DA09439/DA/NIDA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/1',1'-dimethylheptyl-delta(8)-tetrahydrocannabinol-11-oic acid; 0/Analgesics; 1972-08-3/Tetrahydrocannabinol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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