Synthèse et évaluations pharmacologiques de nouveaux inhibiteurs β-lactamiques de la Fatty Acid Amide Hydrolase humaine (hFAAH)
(2012)
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- (en) Research on cannabis effects has evolved in a medicinal context towards the discovery and the understanding of the endocannabinoid system. Most of the effects, beneficial or psychotropic, produced by the cannabis consumption have been ascribed to the activation of two receptors, called cannabinoid receptors CB1 and CB2, by a liposoluble molecule the tetrahydrocannabinol (THC). Displaying the existence of these two receptors has accelerated the research about an eventual endogenous cannabinoid or “endocannabinoid” system which might regulate similar effects (e. g. inflammation modulation, nociception, appetite stimulation). Later, two derivatives of arachidonic acid, the arachidonoylethanolamide (anandamide) and the arachidonylglycerol (2-AG), were isolated and shown to play this role. Indeed, these two neurotransmitters produced “on demand” both activate the cannabinoid receptors which induce various similar physiological effects to those produced by THC, without inducing the psychotropic ones. This last property signs the originality and the advantages of the endocannabinoid versus cannabinoid system. However, to take advantage of endocannabinoid system for therapeutic use (against inflammation or pain), the regulation system of the endogenous ligands, which is composed of degradation enzymes, must be counteract. Fatty Acid Amide Hydrolase (FAAH) and Monoacylglycerol lipase (MAGL) are both responsible of the degradation of anandamide and 2-AG respectively, limiting their action. Our project took place in a highly competitive context where the discovery and synthesis of new inhibitors of FAAH constitutes a real challenge. Successfully, our efforts drove us to the discovery of a novel reversible β-lactamic inhibitor of FAAH. This manuscript is presented as a compilation of a review and three articles published in scientific journals.
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Feledziak, M. (2012). Synthèse et évaluations pharmacologiques de nouveaux inhibiteurs β-lactamiques de la Fatty Acid Amide Hydrolase humaine (hFAAH). https://hdl.handle.net/2078.5/162190