AM404 is an analog of arachidonyl ethanolamide (AEA) which potentiates the activity of endogenous AEA by blocking its re-uptake into presynaptic neurons. AM404 selectively inhibits the carrier-mediated transport of AEA without affecting anandamide hydrolysis. It inhibits the transport of AEA with an IC of 1 µM in rat neurons and 5 µM in rat astrocytes. In in vivo models, AM404 enhances and prolongs exogenous AEA-induced analgesia at a dose of 10 mg/kg.
AM404 an inhibitor of endocannabinoid reuptake, blocks anandamide transport with IC50 values in the low micromolar range. AM404 is able to relax rat isolated hepatic arteries contracted with Phenylephrine, with a pEC50 value of 7.4 (corresponding to an EC50 of 0.04 μM). Neuroprotective Effect.
体外研究
AM404 reduces C6 glioma cell proliferation with IC50 values of 4.9 μM. AM404 non-specifically inhibit C6 glioma cell proliferation at concentrations used to block the cellular accumulation of the endocannabinoid anandamide.
Cell Viability Assay
Cell Line:
Rat C6 glioma cells
Concentration:
1, 3, 10 and 30 µM
Incubation Time:
24, 48, 72 and 96 hours
Result:
Produced a concentration-dependent reduction in cell proliferation that was seen with 24 h of exposure to 10 and 30 µM concentrations and after 48 h at 3 µM. The lowest concentration of AM404 tested, 1 µM, produced a significant, albeit small, reduction in cell proliferation at 72 h.
体内研究
AM404 (1-5 mg/kg, i.p.) exerts dose-dependent anxiolytic-like effects in the three models: elevated plus maze, defensive withdrawal and separation-induced ultrasonic vocalizations.
Animal Model:
Adult male Sprague-Dawley rats (250-300 g)
Dosage:
2.5-10 mg/kg
Administration:
Intraperitoneal (i.p.)
Result:
Caused a dose-dependent increase in anandamide levels in prefrontal cortex, hippocampus and thalamus.