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New insights into endocannabinoid degradation and its therapeutic potential.
Mini Rev Med Chem 2006; 6(3):257-68MR

Abstract

Endocannabinoids are amides, esters and ethers of long chain polyunsaturated fatty acids, which act as new lipidic mediators. Anandamide (N-arachidonoylethanolamine; AEA) and 2-arachidonoylglycerol (2-AG) are the main endogenous agonists of cannabinoid receptors, able to mimic several pharmacological effects of (-)-Delta9-tetrahydrocannabinol (THC), the active principle of Cannabis sativa preparations like hashish and marijuana. The activity of AEA and 2-AG at their receptors is limited by cellular uptake through an anandamide membrane transporter (AMT), followed by intracellular degradation. A fatty acid amide hydrolase (FAAH) is the main AEA hydrolase, whereas a monoacylglycerol lipase (MAGL) is critical in degrading 2-AG. Here, we will review growing evidence that demonstrates that these hydrolases are pivotal regulators of the endogenous levels of AEA and 2-AG in vivo, overall suggesting that specific inhibitors of AMT, FAAH or MAGL may serve as attractive therapeutic targets for the treatment of human disorders. Recently, the N-acylphosphatidylethanolamine-specific phospholipase D (NAPE-PLD), which synthesizes AEA from N-arachidonoylphosphatidylethanolamine (NArPE), and the diacylglycerol lipase (DAGL), which generates 2-AG from diacylglycerol (DAG) substrates, have been characterized. The role of these synthetic routes in maintaining the endocannabinoid tone in vivo will be discussed. Finally, the effects of inhibitors of endocannabinoid degradation in animal models of human disease will be reviewed, with an emphasis on their ongoing applications in anxiety, cancer and neurodegenerative disorders.

Authors+Show Affiliations

Department of Biomedical Sciences, University of Teramo, Teramo, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

16515464

Citation

Bari, M, et al. "New Insights Into Endocannabinoid Degradation and Its Therapeutic Potential." Mini Reviews in Medicinal Chemistry, vol. 6, no. 3, 2006, pp. 257-68.
Bari M, Battista N, Fezza F, et al. New insights into endocannabinoid degradation and its therapeutic potential. Mini Rev Med Chem. 2006;6(3):257-68.
Bari, M., Battista, N., Fezza, F., Gasperi, V., & Maccarrone, M. (2006). New insights into endocannabinoid degradation and its therapeutic potential. Mini Reviews in Medicinal Chemistry, 6(3), pp. 257-68.
Bari M, et al. New Insights Into Endocannabinoid Degradation and Its Therapeutic Potential. Mini Rev Med Chem. 2006;6(3):257-68. PubMed PMID: 16515464.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - New insights into endocannabinoid degradation and its therapeutic potential. AU - Bari,M, AU - Battista,N, AU - Fezza,F, AU - Gasperi,V, AU - Maccarrone,M, PY - 2006/3/7/pubmed PY - 2006/5/26/medline PY - 2006/3/7/entrez SP - 257 EP - 68 JF - Mini reviews in medicinal chemistry JO - Mini Rev Med Chem VL - 6 IS - 3 N2 - Endocannabinoids are amides, esters and ethers of long chain polyunsaturated fatty acids, which act as new lipidic mediators. Anandamide (N-arachidonoylethanolamine; AEA) and 2-arachidonoylglycerol (2-AG) are the main endogenous agonists of cannabinoid receptors, able to mimic several pharmacological effects of (-)-Delta9-tetrahydrocannabinol (THC), the active principle of Cannabis sativa preparations like hashish and marijuana. The activity of AEA and 2-AG at their receptors is limited by cellular uptake through an anandamide membrane transporter (AMT), followed by intracellular degradation. A fatty acid amide hydrolase (FAAH) is the main AEA hydrolase, whereas a monoacylglycerol lipase (MAGL) is critical in degrading 2-AG. Here, we will review growing evidence that demonstrates that these hydrolases are pivotal regulators of the endogenous levels of AEA and 2-AG in vivo, overall suggesting that specific inhibitors of AMT, FAAH or MAGL may serve as attractive therapeutic targets for the treatment of human disorders. Recently, the N-acylphosphatidylethanolamine-specific phospholipase D (NAPE-PLD), which synthesizes AEA from N-arachidonoylphosphatidylethanolamine (NArPE), and the diacylglycerol lipase (DAGL), which generates 2-AG from diacylglycerol (DAG) substrates, have been characterized. The role of these synthetic routes in maintaining the endocannabinoid tone in vivo will be discussed. Finally, the effects of inhibitors of endocannabinoid degradation in animal models of human disease will be reviewed, with an emphasis on their ongoing applications in anxiety, cancer and neurodegenerative disorders. SN - 1389-5575 UR - https://www.unboundmedicine.com/medline/citation/16515464/New_insights_into_endocannabinoid_degradation_and_its_therapeutic_potential_ L2 - http://www.eurekaselect.com/56882/article DB - PRIME DP - Unbound Medicine ER -