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The pharmacology and therapeutic relevance of endocannabinoid derived cyclo-oxygenase (COX)-2 products.
Pharmacol Ther. 2008 Oct; 120(1):71-80.P&T

Abstract

The discovery of anandamide and 2-arachidonyl glycerol (2-AG) as naturally occurring mammalian endocannabinoids has had important and wide-reaching therapeutic implications. This, to a large extent, ensues from the complexity of endocannabinoid biology. One facet of endocannabinoid biology now receiving increased attention is the cyclo-oxygenase-2 (COX-2) derived oxidation products. Anandamide and 2-AG are oxidized to a range of PG-ethanolamides and PG-glyceryl esters that closely approaches that of the prostaglandins (PGs) formed from arachidonic acid. The pharmacology of these electrochemically neutral PG-ethanolamides (prostamides) and PG-glyceryl esters appears to be unique. No meaningful interaction with natural or recombinant prostanoid receptors is apparent. Nevertheless, in certain cells and tissues, prostamides and PG-glyceryl esters exert potent effects. The recent discovery of selective antagonists for the putative prostamide receptor has been a major advance in further establishing prostamide pharmacology as an entity distinct from prostanoid receptors. Since discovery of the prototype prostamide antagonist (AGN 204396), rapid progress has been made. The latest prostamide antagonists (AGN 211334-6) are 100 times more potent than the prototype and are, therefore, sufficiently active to be used in living animal studies. These compounds will allow a full evaluation of the role of prostamides in health and disease. To date, the only therapeutic application for prostamides is in glaucoma. The prostamide analog, bimatoprost, being the most effective ocular hypotensive drug currently available. Interestingly, PGE(2)-glyceryl ester and its chemically stable analog PGE(2)-serinolamide also lower intraocular pressure in dogs. Nevertheless, the therapeutic future of PGE(2)-glyceryl ester is more likely to reside in inflammation.

Authors+Show Affiliations

Allergan Inc., 2525 Dupont Drive, Irvine, CA 92612, USA. woodward_david@allergan.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

18700152

Citation

Woodward, D F., et al. "The Pharmacology and Therapeutic Relevance of Endocannabinoid Derived Cyclo-oxygenase (COX)-2 Products." Pharmacology & Therapeutics, vol. 120, no. 1, 2008, pp. 71-80.
Woodward DF, Carling RW, Cornell CL, et al. The pharmacology and therapeutic relevance of endocannabinoid derived cyclo-oxygenase (COX)-2 products. Pharmacol Ther. 2008;120(1):71-80.
Woodward, D. F., Carling, R. W., Cornell, C. L., Fliri, H. G., Martos, J. L., Pettit, S. N., Liang, Y., & Wang, J. W. (2008). The pharmacology and therapeutic relevance of endocannabinoid derived cyclo-oxygenase (COX)-2 products. Pharmacology & Therapeutics, 120(1), 71-80. https://doi.org/10.1016/j.pharmthera.2008.08.001
Woodward DF, et al. The Pharmacology and Therapeutic Relevance of Endocannabinoid Derived Cyclo-oxygenase (COX)-2 Products. Pharmacol Ther. 2008;120(1):71-80. PubMed PMID: 18700152.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The pharmacology and therapeutic relevance of endocannabinoid derived cyclo-oxygenase (COX)-2 products. AU - Woodward,D F, AU - Carling,R W C, AU - Cornell,C L, AU - Fliri,H G, AU - Martos,J L, AU - Pettit,S N, AU - Liang,Y, AU - Wang,J W, Y1 - 2008/08/06/ PY - 2008/08/01/received PY - 2008/08/01/accepted PY - 2008/8/14/pubmed PY - 2009/1/24/medline PY - 2008/8/14/entrez SP - 71 EP - 80 JF - Pharmacology & therapeutics JO - Pharmacol Ther VL - 120 IS - 1 N2 - The discovery of anandamide and 2-arachidonyl glycerol (2-AG) as naturally occurring mammalian endocannabinoids has had important and wide-reaching therapeutic implications. This, to a large extent, ensues from the complexity of endocannabinoid biology. One facet of endocannabinoid biology now receiving increased attention is the cyclo-oxygenase-2 (COX-2) derived oxidation products. Anandamide and 2-AG are oxidized to a range of PG-ethanolamides and PG-glyceryl esters that closely approaches that of the prostaglandins (PGs) formed from arachidonic acid. The pharmacology of these electrochemically neutral PG-ethanolamides (prostamides) and PG-glyceryl esters appears to be unique. No meaningful interaction with natural or recombinant prostanoid receptors is apparent. Nevertheless, in certain cells and tissues, prostamides and PG-glyceryl esters exert potent effects. The recent discovery of selective antagonists for the putative prostamide receptor has been a major advance in further establishing prostamide pharmacology as an entity distinct from prostanoid receptors. Since discovery of the prototype prostamide antagonist (AGN 204396), rapid progress has been made. The latest prostamide antagonists (AGN 211334-6) are 100 times more potent than the prototype and are, therefore, sufficiently active to be used in living animal studies. These compounds will allow a full evaluation of the role of prostamides in health and disease. To date, the only therapeutic application for prostamides is in glaucoma. The prostamide analog, bimatoprost, being the most effective ocular hypotensive drug currently available. Interestingly, PGE(2)-glyceryl ester and its chemically stable analog PGE(2)-serinolamide also lower intraocular pressure in dogs. Nevertheless, the therapeutic future of PGE(2)-glyceryl ester is more likely to reside in inflammation. SN - 0163-7258 UR - https://www.unboundmedicine.com/medline/citation/18700152/The_pharmacology_and_therapeutic_relevance_of_endocannabinoid_derived_cyclo_oxygenase__COX__2_products_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0163-7258(08)00125-3 DB - PRIME DP - Unbound Medicine ER -