Anxiolytic-like effect of (4-benzylpiperazin-1-yl)(3-methoxyquinoxalin-2-yl)methanone (6g) in experimental mouse models of anxiety

Abstract

Aim:The present study was designed to investigate the anxiolytic activity of 6g, a novel serotonin type-3 receptor (5-HT3) receptor antagonist in experimental mouse models of anxiety.Materials and Methods:The anxiolytic activity of “6g” (1 and 2 mg/kg, intraperitoneally [i.p.]) was evaluated in mice by using a battery of behavioral tests of anxiety such as elevated plus maze (EPM), light-dark (L&D) box, hole board (HB), and open field test (OFT) with diazepam (2 mg/kg, i.p.) as standard anxiolytic. None of the tested dose of “6g” affects the base line locomotion.Results:The new chemical entity “6g” (2 mg/kg, i.p.) and diazepam (2 mg/kg, i.p.) significantly (P < 0.05) increased the percentage of time spent and number of entries in open arm in the EPM test. In the L&D test compound “6g” (2 mg/kg, i.p.) and diazepam (2 mg/kg, i.p.) significantly (P < 0.05) increased the total time spent in light compartment as well as number of transitions from one compartment to other. Compound “6g” (1 and 2 mg/kg, i.p.) and diazepam (2 mg/kg, i.p.) also significantly (P < 0.05) increased number of head dips, whereas significantly (P < 0.05) decreased the head dipping latency in HB test as compared to vehicle control group. In addition, 6g (2 mg/kg, i.p.) and diazepam (2 mg/kg, i.p.) significantly (P < 0.05) increased the ambulation scores (square crossed) in OFT and there was no significant effect of 6g (1 and 2 mg/kg, i.p.) and diazepam (2 mg/kg, i.p.) on rearing scores.Conclusion:In conclusion, these findings indicated that compound “6g” exhibited an anxiolytic-like effect in animal models of anxiety.

Neuropharmacological evaluation of a novel 5-HT3 receptor antagonist (4-benzylpiperazin-1-yl)(3-methoxyquinoxalin-2-yl) methanone (6g) on lipopolysaccharide-induced anxiety models in mice

“…A compartment entry was considered valid when the animal's all four paws were inside that chamber. The apparatus was thoroughly cleaned with 70% ethanol after each trial [14].…”

“…The ambulation scores (number of square crossed) and rearing number (standing upright on hind legs) were recorded for 5 min period. After each individual test session the floor was thoroughly cleaned with 70% ethanol [14,18].…”

“…Increased availability of 5-HT over 5-HT 2 and 5-HT 3 receptors increases anxiety, while blockade of 5-HT 3 receptors produces anxiolytic-like effect [10,11]. Several preclinical and clinical studies have suggested that 5-HT 3 receptors may be a relevant target in the treatment of affective disorders such as anxiety and depression [11][12][13][14].…”

“…Despite preclinical screening of compound 6g for its antidepressant and anxiolytic potential in various rodent models, the effect of compound 6g in LPS-induced anxiety is yet to be explored to identify its potential usefulness in the treatment/prevention of anxiety disorder [14]. Therefore, the present study was designed to explore the anxiolytic-like effect of compound 6g in LPS-induced anxiety model in mice.…”

Neuro-pharmacological evaluation of structurally novel 5-hydroxytryptamine type 3 receptor antagonist, N-n-propyl-3-ethoxyquinoxaline-2-carboxamide (6n) for its anxiolytic potential

“…Previous reports suggested that anxiolytic compound have a tendency to reduce the fearful behaviors of rodents in open field. [28] "6n" treatment increased the ambulation scores in OFT indicating the anxiolytic effect of "6n. "…”