Agomelatine, a multi-target drug, does not alter basal locomotor activity in rats

Generally, the initial treatment for patients with depressive disorder is the dosage of antidepressants with sedative-hypnotic activity. However, these antidepressant medications, due to their sedative effects, limit the daytime activities of patients. Therefore, it is required to develop antidepressants that promote sleep but do not generate adverse daytime effects. Agomelatine is an antidepressant that improves sleep quality through a mechanism that does not involve sedative-hypnotic effects. However, no study evaluates agomelatine-induced sedative-hypnotic effects. The purpose of this study was to assess the impact of agomelatine administered at different times of day on the magnitude of the sedative-hypnotic activity of different agomelatine doses (5, 10, and 40 mg/kg) in rats.

Sedation was assessed in Wistar rats behaviorally, using rota-rod, spontaneous locomotor activity, and fixed-bar tests at different times of day (ZT4, ZT10, ZT16, and ZT22). Agomelatine was dosed at 5, 10, and 40 mg/kg.

Our results showed that, compared to trazodone, acute and chronic dosing of ≤40 mg/kg agomelatine produced mild, transient sedative effects. In contrast, doses of ≥10 mg/kg did not cause sustained sedative effects.

These results suggest that agomelatine, at different doses, does not cause sustained sedation but may transiently suppress locomotion at higher doses.