Document Detail

A structure-activity relationship study on N-arachidonoyl-amino acids as possible endogenous inhibitors of fatty acid amide hydrolase.
MedLine Citation:
PMID:  14715265     Owner:  NLM     Status:  MEDLINE    
N-arachidonoyl-glycine (NAGly) has been recently identified in rodent tissues and found to exhibit analgesic activity in vivo. NAGly is a potent inhibitor of the fatty acid amide hydrolase (FAAH), the enzyme primarily responsible for the degradation of the endocannabinoid N-arachidonoyl-ethanolamine (anandamide), and was shown recently to elevate the blood levels of the this analgesic compound. We have synthesized several N-arachidonoyl-amino acids of potential natural occurrence, as well as the D- and L-isomers of N-arachidonoyl-alanine, and have tested their activity on FAAH preparations from mouse, rat, and human cell lines, and from mouse or rat brain. The results indicate that the relative potency and enantioselectivity of N-arachidonoyl-amino acids as FAAH inhibitors depend on the animal species. Thus, whilst NAGly is the most potent compound on the rat and mouse enzymes, N-arachidonoyl-isoleucine is active only on human FAAH and N-arachidonoyl-alanine enantiomers show a varying degree of potency. Taken together, these data support the view that an enhancement of endogenous anandamide levels underlies in part the analgesic effects of NAGly in rodents.
Maria Grazia Cascio; Alberto Minassi; Alessia Ligresti; Giovanni Appendino; Sumner Burstein; Vincenzo Di Marzo
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  314     ISSN:  0006-291X     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2004 Jan 
Date Detail:
Created Date:  2004-01-12     Completed Date:  2004-04-19     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  192-6     Citation Subset:  IM    
Endocannabinoid Research Group, Istituto di Chimica Biomolecolare, CNR, Via Campi Flegrei 34, Comprensorio A. Olivetti, Building 70, 80078 Pozzuoli (NA), Italy.
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MeSH Terms
Alanine / analogs & derivatives,  chemistry*
Amidohydrolases / antagonists & inhibitors*,  chemistry
Amino Acids / chemistry
Arachidonic Acids / chemistry*
Glycine / analogs & derivatives*,  chemistry*
Species Specificity
Structure-Activity Relationship*
Substrate Specificity
gamma-Aminobutyric Acid / analogs & derivatives,  chemistry*
Grant Support
Reg. No./Substance:
0/Amino Acids; 0/Arachidonic Acids; 0/N-arachidonoyl-gamma-amino-butyric acid; 0/N-arachidonoylalanine; 0/N-arachidonylglycine; 56-12-2/gamma-Aminobutyric Acid; 56-40-6/Glycine; 56-41-7/Alanine; EC 3.5.-/Amidohydrolases; EC 3.5.1.-/fatty-acid amide hydrolase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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