AM4113, a pyrazole analog structurally related to SR141716 and AM251, is a novel cannabinoid CB1 neutral antagonist. AM4113 suppressed food intake and food-reinforced behavior in rats.
In vitro: AM4113 was able to bind with high affinity to CB1 receptors, exhibiting 100-fold selectivity for CB1 against CB2 receptors. The Ki value for CB1 was 0.897 ± 0.44 nM, while the Ki value for hCB2 was 92 ± 6.9 nM [1].
In vivo: In rats, treatment with AM4113 (2.0 and 4.0 mg/kg) attenuated the AM411-induced locomotor suppression and analgesia. In addition, 4.0 mg/kg AM4113 alone significantly suppressed locomotor activity when compared with vehicle. AM4113 dose-dependently decreased lever pressing on an FR1 schedule. AM4113 produced conditioned taste avoidance and suppression of ingestive (hedonic) taste reactivity scores in a dose-dependent manner [1]. AM4113 didn’t induce signs of nausea [1].
Reference:
[1] Sink K S, McLaughlin P J, Wood J A T, et al. The novel cannabinoid CB1 receptor neutral antagonist AM4113 suppresses food intake and food-reinforced behavior but does not induce signs of nausea in rats[J]. Neuropsychopharmacology, 2008, 33(4): 946-955.