TY - JOUR
T1 - The novel cannabinoid CB1 antagonist AM6545 suppresses food intake and food-reinforced behavior
AU - Randall, P. A.
AU - Vemuri, V. K.
AU - Segovia, K. N.
AU - Torres, E. Ferreris
AU - Hosmer, S.
AU - Nunes, E. J.
AU - Santerre, J. L.
AU - Makriyannis, A.
AU - Salamone, J. D.
N1 - Funding Information:
This research was supported by grants to JDS and AM from the United States NIH / NIDA .
PY - 2010/11
Y1 - 2010/11
N2 - Drugs that interfere with cannabinoid CB1 transmission suppress food-motivated behaviors, and may be useful clinically as appetite suppressants. However, there may also be undesirable side effects (e.g., nausea, malaise, anxiety, and depression) that are produced by the current generation of CB1 inverse agonists such as rimonabant and taranabant. For that reason, it is important to continue research on novel cannabinoid antagonists. The present studies examined the effects of the novel compound AM6545, which is a neutral antagonist of CB1 receptors that is thought to have relatively poor penetrability into the central nervous system. Intraperitoneal administration of AM6545 significantly reduced food-reinforced operant responding at doses of 4.0, 8.0 and 16.0. mg/kg. AM6545 also produced a strong suppression of the intake of high-carbohydrate and high-fat diets in the same dose range, but only produced a mild suppression of lab chow intake at the highest dose (16.0. mg/kg). Although AM6545 did not affect food handling, it did reduce time spent feeding and feeding rate. Taken together, these results suggest that AM6545 is a compound that warrants further study as a potential appetite suppressant drug.
AB - Drugs that interfere with cannabinoid CB1 transmission suppress food-motivated behaviors, and may be useful clinically as appetite suppressants. However, there may also be undesirable side effects (e.g., nausea, malaise, anxiety, and depression) that are produced by the current generation of CB1 inverse agonists such as rimonabant and taranabant. For that reason, it is important to continue research on novel cannabinoid antagonists. The present studies examined the effects of the novel compound AM6545, which is a neutral antagonist of CB1 receptors that is thought to have relatively poor penetrability into the central nervous system. Intraperitoneal administration of AM6545 significantly reduced food-reinforced operant responding at doses of 4.0, 8.0 and 16.0. mg/kg. AM6545 also produced a strong suppression of the intake of high-carbohydrate and high-fat diets in the same dose range, but only produced a mild suppression of lab chow intake at the highest dose (16.0. mg/kg). Although AM6545 did not affect food handling, it did reduce time spent feeding and feeding rate. Taken together, these results suggest that AM6545 is a compound that warrants further study as a potential appetite suppressant drug.
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U2 - 10.1016/j.pbb.2010.07.021
DO - 10.1016/j.pbb.2010.07.021
M3 - Article
C2 - 20713079
AN - SCOPUS:77957749920
SN - 0091-3057
VL - 97
SP - 179
EP - 184
JO - Pharmacology Biochemistry and Behavior
JF - Pharmacology Biochemistry and Behavior
IS - 1
ER -