Synthesis and characterizations of novel quinoline derivatives having mixed ligand activities at the κ and μ receptors: Potential therapeutic efficacy against morphine dependence

Abstract Based on an established 3D pharmacophore, a series of quinoline derivatives were synthesized. The opioidergic properties of these compounds were determined by a competitive binding assay using 125 I-Dynorphine, 3 H-DAMGO and 125 I-DADLE for κ, μ, and δ receptors, respectively. Results showed varying degree of activities of the compounds to κ and μ opioid receptors with negligible interactions at the δ receptor. The compound, S4 was the most successful in inhibiting the two most prominent quantitative features of naloxone precipitated withdrawal symptoms - stereotyped jumping and body weight loss. Determination of IC 50 of S4 revealed a greater affinity towards μ compared to κ receptor. In conclusion, quinoline derivatives of S4 like structure offer potential tool for treatment of narcotic addictions.