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ABSTRACT
Characterization of [3-(3-carbamoylphenyl) phenyl] N- cyclohexyl carbamate, an inhibitor of FAAH: effect on rat liver FAAH and HEK293T-FAAH-2 deamination of oleamide, arachidonamide and stearoylamide
Julius T. Dongdem
ABSTRACT
he carbamate, [3-(3-carbamoylphenyl) phenyl] N-cyclohexyl carbamate (URB597) is a known irreversible inhibitor of fatty acid amide hydrolase (FAAH) which is capable of increasing intracellular endocannabinoid levels to measurable antidepressant and analgesic effects in animal models. Several endocannabinoid-like compounds such as the primary fatty acid amides (PFAMs) are also important signaling molecules which control many physiological processes and exhibit the characteristic cannabimimetics though the physiological functions of some remain elusive. Thus, PEFAMs remain candidates for examination. Since the initial discovery of URB597, little has been reported on its ability to inhibit the FAAH-dependent metabolism of important PFAM substrates. Also, the mode of inhibition of FAAH hydrolysis of substrates by URB597 has not been characterized. FAAH-2 was expressed in HEK293T cells whereas FAAH was assayed from rat liver preparations. Activity assay employed was a modification of a high throughput fluorimetric screening method’.
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