Description
The central cannabinoid (CB
1) receptor is a G protein-
coupled receptor that is widely distributed in the central nervous system and several peripheral tissues and binds the active component of cannabis, Δ
9-
tetrahydrocannabinol. Signaling through the CB
1 receptor is implicated in attentional and working memory deficits as well as obesity. AVE-
1625 is a highly potent, selective antagonist for the CB
1 receptor with K
i values of 0.16-
0.44 nM. At 1-
3 mg/kg, AVE-
1625 significantly improves the performance of rodents in working memory tasks. At 30 mg/kg, AVE-
1625 reduces caloric intake by more than 50% of controls and significantly increases lipolysis from fat tissues and reduces hepatic glycogen levels in rodents.
in vivo
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 in
their 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.
|
References
[1] borowsky b, stevens r, mark b, et al. ave1625, a cannabinoid cbi antagonist, as a co-treatment for schizophrenia: improvement in cognitive function and reduction of antipsychotic-side effects in animal models[c]//neuropsychopharmacology. macmillan building, 4 crinan st, london n1 9xw, england: nature publishing group, 2005, 30: s116-s117.
[2] herkenham m, lynn a b, little m d, et al. cannabinoid receptor localization in brain[j]. proceedings of the national academy of sciences, 1990, 87(5): 1932-1936.
[3] herling a w, gossel m, haschke g, et al. cb1 receptor antagonist ave1625 affects primarily metabolic parameters independently of reduced food intake in wistar rats[j]. american journal of physiology-endocrinology and metabolism, 2007, 293(3): e826-e832.
