Pharmacological evaluation of novel 5-HT₃ receptor antagonist, QCM-13 (N-cyclohexyl-3-methoxyquinoxalin-2-carboxamide) as anti-anxiety agent in behavioral test battery

Objective: In the last few decades, serotonin type-3 (5-HT₃ ) receptor antagonists have been identified as potential targets for anxiety disorders. In preclinical studies, 5-HT₃ antagonists have shown promising antianxiety effects. In this study, a novel 5-HT₃ receptor antagonist, QCM-13(N-cyclohexyl-3-methoxyquinoxalin-2-carboxamide) was evaluated for anxiolytic-like activity in rodent behavioral test battery. Materials and Methods: Mice were given QCM-13 (2 and 4 mg/kg, intraperitoneally [i.p.]) or diazepam (2 mg/kg, i.p.) or vehicle and after 30 min, mice were subjected to four validated behavioral test batteries viz. elevated plus maze, hole board, light-dark and open field tests. Interaction study of QCM-13 with m-chlorophenyl piperazine (mCPP) (mCPP, a 5-HT_2A/2C receptor agonist, 1 mg/kg, i.p.) and buspirone (BUS, a partial 5-HT_1A agonist, 10 mg/kg, i.p.) were performed to assess the pharmacological mechanism of the drug. Results: QCM-13 expressed potential anxiolytic effect with significant (P < 0.05) increase in behavioral parameters measured in aforementioned preliminary models. Besides, QCM-13 was unable to reverse the anxiogenic effect of mCPP, but potentiated anxiolytic affect of BUS. Conclusion: The results suggest that QCM-13 can be a potential therapeutic candidate for the management of anxiety-like disorders and combination doses of novel 5-HT₃ receptor antagonist with standard anxiolytics may improve therapeutic efficacy.