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Overview
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Background
CP 945598 hydrochloride is a selective and high affinity CB1 antagonist with Ki value of 0.7 and 0.12 nM for binding and functional assays, respectively [1]. The CB1 receptor is a G protein-coupled cannabinoid receptor located primarily in the central and peripheral nervous system and plays an important role in energy homeostasis.CP 945598 dose-dependently reversed the four characteristic effects (hypothermia, anti-nociception, hypo-locomotion, and catalepsy) of a centrally acting cannabinoid agonist (CP 55940). In mice model, CP 945598 (17.8 mg/kg s.c.) increased locomotor activity. In Sprague–Dawley rats, CP 945598 reduced food intake in a dose and concentration dependent way. With doses of 10 mg/kg and 30 mg/kg, CP 945598 increased energy expenditure by 16% and 19%, respectively. Also, ex vivo brain receptor occupancy increased to 33–36% in a dose-related way. In diet-induced obese mice, CP 945598 significantly decreased body weight by 9% compared to vehicle-treated mice [2].
[1]. Griffith DA, Hadcock JR, Black SC, et al. Discovery of 1-[9-(4-Chlorophenyl)-8-(2-chlorophenyl)-9H-purin-6-yl]-4-ethylaminopiperidine-4-carboxylic acid amide hydrochloride (CP-945,598), a novel, potent, and selective cannabinoid type 1 receptor antagonist. J Med Chem, 2009, 52(2): 234-237.
[2]. Hadcock JR1, Griffith DA, Iredale PA, et al. In vitro and in vivo pharmacology of CP-945,598, a potent and selective cannabinoid CB1 receptor antagonist for the management of obesity. Biochem Biophys Res Commun, 2010, 394(2): 366-371.
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