Oximes short-acting CB1 receptor agonists

The novel cannabinoid CB1 receptor agonist AM11101 increases food intake in female rats

“…A within‐subjects, randomized design was used to examine the effects of vehicle, AM11101 (0.01, 0.05, and 0.1 mg·kg −1 ), and THC (1 mg·kg −1 ) on chow intake in pre‐fed animals ( n = 8). Doses of AM11101 were chosen based on the increased potency of AM11101 over THC in various in vitro assays (Malamas et al, ). The single dose of THC (1 mg·kg −1 ) was chosen because it was found to be the maximally effective orexigenic dose in Experiment 1.…”

“…THC (5 mg·mL −1 ; dissolved in 100% ethanol) was provided by the National Institute of Drug Abuse (NIDA, Bethesda, MD). The novel CB 1 receptor agonist AM11101 (1 mg·mL −1 ; dissolved in 100% ethanol) was synthesized and provided by the Center for Drug Discovery (Northeastern University, Boston, MA; Malamas et al, ). Stock solutions of both compounds were stored at −20°C.…”

“…The propensity for THC and other cannabinoids to become sequestered in adipose tissue, resulting in unpredictable actions in various animal models, highlights the need to develop novel compounds that target CB 1 receptors with a more predictable pharmacological action and fewer unwanted side effects than THC and its congeners. To this end, a drug design strategy was used to develop a novel cannabinoid compound, termed AM11101, which was synthesized via the introduction of internal polar moieties at both the C3 position and terminal carbon of the alkyl tail of Δ 8 ‐tetrahydrocannabinol (Δ 8 ‐THC; Malamas et al, ; AM11101 is compound 8a). Pharmacological screening of this new compound has shown that AM11101 acts as a partial agonist at CB 1 receptors with a decreased lipophilic character and a greater CB 1 receptor binding affinity than Δ 8 ‐THC (Malamas et al, ).…”

“…To this end, a drug design strategy was used to develop a novel cannabinoid compound, termed AM11101, which was synthesized via the introduction of internal polar moieties at both the C3 position and terminal carbon of the alkyl tail of Δ 8 ‐tetrahydrocannabinol (Δ 8 ‐THC; Malamas et al, ; AM11101 is compound 8a). Pharmacological screening of this new compound has shown that AM11101 acts as a partial agonist at CB 1 receptors with a decreased lipophilic character and a greater CB 1 receptor binding affinity than Δ 8 ‐THC (Malamas et al, ). Here, we provide the first analysis of AM11101's ability to stimulate feeding behaviour in a rodent model.…”

“…Food intake and meal patterns were also examined following chronic (7‐day) treatment with AM11101 or THC. Based on the presumed improvement in druggability of AM11101 (Malamas et al, ), we hypothesized that AM11101 would increase food intake in all test conditions and that its orexigenic effect may be larger or more reliable than that observed in response to THC treatment.…”