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Focus on the three key enzymes hydrolysing endocannabinoids as new drug targets.
Curr Pharm Des 2005; 11(20):2647-68CP

Abstract

The family of endocannabinoids (i.e., the endogenous agonists of cannabinoid receptors) contains several polyunsaturated fatty acid amides such as anandamide (AEA) and oleamide but also esters such as 2-arachidonoylglycerol (2-AG). These compounds are the subject of growing interest in pharmacology for their multiple therapeutic potentials. Unfortunately, they are rapidly inactivated by enzymatic hydrolysis, which prevents their effective medical use. Inhibitors of endocannabinoid degradation seem to be necessary tools for the development of endocannabinoid therapeutics. But hitting this target is inconceivable without good knowledge of the enzymes. Fatty acid amide hydrolase (FAAH) is the oldest and the best characterised enzyme involved in the degradation of endocannabinoids. Cloning, distribution in the body and crystal structure of FAAH have been described. A large number of FAAH inhibitors have also been synthesised and tested. For a long time, FAAH was considered as the only key enzyme hydrolysing endocannabinoids. But recent findings indicate that at least two other enzymes have critical role in the endocannabinoids degradation. Monoglyceride lipase participates in 2-AG degradation and some data indicate that it is the primary mechanism for 2-AG inactivation in intact neurons. N-palmitoylethanolamine-selective acid amidase (NPAA) is a second fatty acid amide hydrolase more active with N-palmitoylethanolamine, an anti-inflammatory substance. The purpose of this review is to collect and compare the catalytic properties of these 3 key enzymes hydrolysing endocannabinoids.

Authors+Show Affiliations

Unité de Chimie Pharmaceutique et de Radiopharmacie, Université catholique de Louvain, Avenue E. Mounier, 73, UCL-CMFA 73-40, B-1200 Brussels, Belgium.No affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Review

Language

eng

PubMed ID

16101463

Citation

Vandevoorde, Séverine, and Didier M. Lambert. "Focus On the Three Key Enzymes Hydrolysing Endocannabinoids as New Drug Targets." Current Pharmaceutical Design, vol. 11, no. 20, 2005, pp. 2647-68.
Vandevoorde S, Lambert DM. Focus on the three key enzymes hydrolysing endocannabinoids as new drug targets. Curr Pharm Des. 2005;11(20):2647-68.
Vandevoorde, S., & Lambert, D. M. (2005). Focus on the three key enzymes hydrolysing endocannabinoids as new drug targets. Current Pharmaceutical Design, 11(20), pp. 2647-68.
Vandevoorde S, Lambert DM. Focus On the Three Key Enzymes Hydrolysing Endocannabinoids as New Drug Targets. Curr Pharm Des. 2005;11(20):2647-68. PubMed PMID: 16101463.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Focus on the three key enzymes hydrolysing endocannabinoids as new drug targets. AU - Vandevoorde,Séverine, AU - Lambert,Didier M, PY - 2005/8/17/pubmed PY - 2006/4/11/medline PY - 2005/8/17/entrez SP - 2647 EP - 68 JF - Current pharmaceutical design JO - Curr. Pharm. Des. VL - 11 IS - 20 N2 - The family of endocannabinoids (i.e., the endogenous agonists of cannabinoid receptors) contains several polyunsaturated fatty acid amides such as anandamide (AEA) and oleamide but also esters such as 2-arachidonoylglycerol (2-AG). These compounds are the subject of growing interest in pharmacology for their multiple therapeutic potentials. Unfortunately, they are rapidly inactivated by enzymatic hydrolysis, which prevents their effective medical use. Inhibitors of endocannabinoid degradation seem to be necessary tools for the development of endocannabinoid therapeutics. But hitting this target is inconceivable without good knowledge of the enzymes. Fatty acid amide hydrolase (FAAH) is the oldest and the best characterised enzyme involved in the degradation of endocannabinoids. Cloning, distribution in the body and crystal structure of FAAH have been described. A large number of FAAH inhibitors have also been synthesised and tested. For a long time, FAAH was considered as the only key enzyme hydrolysing endocannabinoids. But recent findings indicate that at least two other enzymes have critical role in the endocannabinoids degradation. Monoglyceride lipase participates in 2-AG degradation and some data indicate that it is the primary mechanism for 2-AG inactivation in intact neurons. N-palmitoylethanolamine-selective acid amidase (NPAA) is a second fatty acid amide hydrolase more active with N-palmitoylethanolamine, an anti-inflammatory substance. The purpose of this review is to collect and compare the catalytic properties of these 3 key enzymes hydrolysing endocannabinoids. SN - 1381-6128 UR - https://www.unboundmedicine.com/medline/citation/16101463/Focus_on_the_three_key_enzymes_hydrolysing_endocannabinoids_as_new_drug_targets_ L2 - http://www.eurekaselect.com/61239/article DB - PRIME DP - Unbound Medicine ER -