AVE 1625

Drinabant (AVE1625) is an orally active CB1 receptor antagonist. Drinabant (AVE1625) inhibits the agonist-stimulated calcium signal with IC50 values of 25 nM and 10 nM for the hCB1-R and rCB1-R, respectively, and is ineffective for the hCB2-R[1].

Research Areas >> Metabolic Disease

Signaling Pathways >> GPCR/G Protein >> Cannabinoid Receptor

hCB1-R:25 nM (IC50)

rCB1-R:10 nM (IC50)

CB2:10000 nM (IC50)

AVE1625 (10 mg/kg orally once daily), combined with Olanzapine (HY-14541) attenuates body weight gain, diminishing the enhanced food intake while maintaining increased energy expenditure and decreased motility[2]. AVE1625 (1, 3, and 10 mg/kg ip), reverses abnormally persistent LI induced by MK-801 (HY-15084B) or neonatal nitric oxide synthase inhibition in rodents, and improves both working and episodic memory[3]. Animal Model: Rats[1]. Dosage: 30 mg/kg. Administration: Oral gavage, single dose. Result: Had free access to food during the preceding night (postprandial state) caused a pronounced reduction of food intake during the subsequent 10-12 h without differences intheir locomotor activity relative to that of the control group. Caused an increase in FFA and glycerol, indicating increased lipolysis from fat tissue. Immediately resulted in a pronounced increase in VCO2 and VO2, indicating increased oxidation of energetic substrates and increased TEE. Animal Model: Female Hanover Wistar rats weighing 225 ± 8.6 g[2]. Dosage: 10 mg/kg. Administration: Orally once daily. Result: Reduced their weight markedly within the first 3 days of treatment where upon animals maintained lower body weight, although they lost about 7.3 ± 1.3 g fat during the 12 days of treatment.

[1]. Andreas W Herling, et al. CB1 receptor antagonist AVE1625 affects primarily metabolic parameters independently of reduced food intake in Wistar rats. Am J Physiol Endocrinol Metab. 2007 Sep;293(3):E826-32.

[2]. Michaela Liebig, et al. Profiling of energy metabolism in olanzapine-induced weight gain in rats and its prevention by the CB1-antagonist AVE1625. Obesity (Silver Spring). 2010 Oct;18(10):1952-8.

[3]. Mark D Black, et al. AVE1625, a cannabinoid CB1 receptor antagonist, as a co-treatment with antipsychotics for schizophrenia: improvement in cognitive function and reduction of antipsychotic-side effects in rodents. Psychopharmacology (Berl). 2011 May;215(1):149-63.