A novel monoacylglycerol lipase inhibitor with analgesic and anti-inflammatory activity.
A variety of long chain 1,2-diamines and related compounds were synthesized and tested for their activity on fatty acid amide hydrolase (FAAH) and monoacyglycerol lipase (MGL). (2S,9Z)-Octadec-9-ene-1,2-diamine selectively inhibits MGL (K(i) 21.8 microM) without significantly affecting FAAH. This compound exhibited interesting in vivo analgesic and anti-inflammatory properties, suggesting that selective inhibitors of MGL may be valuable novel agents for the treatment of inflammatory pain.
Magrioti
Victoria
V
Laboratory of Organic Chemistry, Department of Chemistry, University of Athens, Panepistimiopolis, Athens 15771, Greece.
Naxakis
George
G
Hadjipavlou-Litina
Dimitra
D
Makriyannis
Alexandros
A
Kokotos
George
G
D000581:Amidohydrolases / Q000737:chemistry; D000700:Analgesics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D063385:Cannabinoid Receptor Modulators / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007213:Indomethacin / Q000737:chemistry; D007249:Inflammation; D007700:Kinetics; D008956:Models, Chemical; D008994:Monoacylglycerol Lipases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D051381:Rats; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D000700:Analgesics; D000893:Anti-Inflammatory Agents; D001241:Aspirin; D063385:Cannabinoid Receptor Modulators; D004791:Enzyme Inhibitors; D007213:Indomethacin; D008994:Monoacylglycerol Lipases; D000099252:Fatty Acid Amide Hydrolases