Open AccessBehavioral effects of the cannabinoid CB 1 receptor allosteric modulator ORG27569 in rats
Author(s) -
Ding Yuanyuan,
Qiu Yanyan,
Jing Li,
Thorn David A.,
Zhang Yanan,
Li JunXu
Publication year - 2014
Publication title -
pharmacology research and perspectives
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.975
H-Index - 27
ISSN - 2052-1707
DOI - 10.1002/prp2.69
Subject(s) - allosteric modulator , allosteric regulation , pharmacology , cannabinoid , cannabinoid receptor , neuroscience , medicine , chemistry , receptor , psychology , agonist
Abstract The cannabinoid CB 1 receptor system is involved in feeding behaviors and the CB 1 receptor antagonist SR 141716A is an effective antiobesity drug. However, SR 141716A also has serious side effects, which prompted the exploration of alternative strategies to modulate this important drug target. Recently a CB 1 receptor allosteric modulating site has been discovered and the allosteric modulating activity of several modulators including ORG 27569 has been characterized in vitro. Yet, little is known of the in vivo pharmacological effects of ORG 27569. This study examined the behavioral pharmacology of ORG 27569 in rats. ORG 27569 (3.2–10 mg/kg, i.p.) selectively attenuated the hypothermic effects of CB 1 receptor agonists CP 55940 (0.1–1 mg/kg) and anandamide (3.2–32 mg/kg). In contrast, SR 141716A only attenuated the hypothermic effects of CP 55940 but not anandamide. SR 141716A but not ORG 27569 blocked CP 55940‐induced catalepsy and antinociception. In addition, ORG 27569 did not modify SR 141716A‐elicited grooming and scratching behaviors. In feeding studies, ORG 27569 decreased palatable and plain food intake which was partially blocked by CP 55940. The hypophagic effect of ORG 27569 developed tolerance after 4 days of daily 5.6 mg/kg treatment; however, the effect on body weight gain outlasted the drug treatment for 10 days. These data suggest that ORG 27569 may not function as a CB 1 receptor allosteric modulator in vivo, although its hypophagic activity still has potential therapeutic utility.