Program in Neuroscience, Department of Psychology, Florida State University, Tallahassee, Florida.
Center for Drug Discovery, Departments of Chemistry, Chemical Biology, and Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts.
Br J Pharmacol. 2019 Oct;176(20):3972-3982. doi: 10.1111/bph.14797. Epub 2019 Sep 6.
Δ -tetrahydrocannabinol (THC) acts via cannabinoid CB receptors to increase feeding. Here, we assessed the orexigenic effect of AM11101, a novel CB receptor agonist designed to have a more favourable pharmacodynamic profile than THC.
The acute, orexigenic effects of AM11101 and THC were compared in female rats. Food intake and meal patterns were also examined following once daily treatment with AM11101 and THC for 7 days.
AM11101 (0.01-0.1 mg·kg ) increased food intake during the first hour following both acute and chronic treatments in pre-fed and freely feeding animals. This orexigenic effect persisted for up to 4 hr, with no compensatory decrease in feeding during the subsequent 4-22 hr. THC (1 mg·kg ) increased 1-hr food intake in pre-fed animals, but was less reliable than AM11101 in increasing 1-hr food intake in freely feeding animals following both acute and chronic administration. The orexigenic effect of both compounds was due to an increase in meal size, not meal number.
Our study provides the first demonstration that AM11101 increases short-term food intake via a selective increase in meal size. AM11101 promotes a more reliable orexigenic effect than THC in freely feeding animals, with no subsequent compensatory decrease in feeding. AM11101 may offer a greater efficacy than THC and its congeners in stimulating food intake in underweight clinical populations.
Δ-四氢大麻酚(THC)通过大麻素 CB 受体作用增加摄食。在此,我们评估了新型 CB 受体激动剂 AM11101 的促食欲作用,该激动剂设计的药效学特征优于 THC。
比较了 AM11101 和 THC 对雌性大鼠的急性、促食欲作用。还在 AM11101 和 THC 每日治疗 7 天后,检查了单次和慢性治疗后的摄食和进食模式。
AM11101(0.01-0.1mg·kg )在预饲和自由摄食动物中,在急性和慢性治疗后第一个小时内增加了食物摄入量。这种食欲增加作用持续长达 4 小时,随后 4-22 小时内摄食量没有补偿性减少。THC(1mg·kg )增加了预饲动物 1 小时的食物摄入量,但在急性和慢性给药后,在自由摄食动物中增加 1 小时的食物摄入量不如 AM11101可靠。两种化合物的促食欲作用是由于进食量的增加,而不是进食次数的增加。
我们的研究首次证明 AM11101 通过选择性增加进食量来增加短期食物摄入量。与 THC 相比,AM11101 在自由摄食动物中产生更可靠的食欲增加作用,随后没有摄食量的补偿性减少。AM11101 在刺激体重不足的临床人群的食物摄入方面可能比 THC 及其同系物更有效。