The novel kappa opioid receptor antagonist CERC-501 attenuates alcohol seeking and withdrawal anxiety

Considerable evidence suggests that kappa opioid receptors (KORs) and their endogenous ligand dynorphin (DYN), play an important role in stress responses, anxiety, depression and addiction related behaviors. In rats, the (DYN)/(KOR) system undergoes ethanol-induced neuroadaptations and results in excessive operant self-administration as well as negative affective-like states. Preclinical data show that JDTic, a selective KOR antagonist reduced alcohol drinking and cue induced reinstatement. More recently, CERC-501 (previously LY2456302), [(S)-3-fluoro-4-(4-((2-(3, 5-dimethylphenyl) pyrrolidin-1 yl) methyl) phenyl)benzamide]), a highly selective and centrally penetrant canonical KOR antagonist has been shown to reduce EtOH self-administration in alcohol preferring rats both after acute and chronic administration at doses that selectively occupied KORs in vivo.

Source: Alcohol - May 1, 2017 Category: Addiction Authors: E. Domi, D. Gehlert, E. Barbier, E. Augier, G. Augier, H. Malm, A.M.A. Aziz, A. Thorsell, M. Heilig Source Type: research