Agomelatine is Superior to Melatonin in Pain Suppression

Objective: Agomelatine is a synthetic analog of melatonin with selective agonist action on melatonin MT1 and MT2 receptors and antagonistic effect on serotonin 5HT2c receptors. Similar to melatonin, it also has antinociceptive properties. There are only a few studies comparing the antinociceptive effects of agomelatine to melatonin. Methods: Male Wistar albino rats were grouped into seven treatment groups and a control group (8 animals each). Treatment groups received intraperitoneal injections of agomelatine 25 mg/kg, 35 mg/kg and 50 mg/kg; agomelatine 35 mg/kg + luzindole 10 mg/kg; melatonin 60 mg/kg and 90 mg/kg and melatonin 60 mg/kg + sertraline 10 mg/kg. Animals were placed on a hot plate and time to pain avoidance behavior was measured. Results: Agomelatine 25 mg/kg, 35 mg/kg and 50 mg/kg were significantly superior to placebo (all p < 0. 0001); agomelatine 35 mg/kg and 50 mg/kg were significantly superior to melatonin 60 mg/kg (p < 0.05 and p < 0.01, respectively) and melatonin 90 mg/kg (p < 0.001 and p < 0.001, respectively) in prolonging reaction times. Agomelatine 50 mg/kg was superior to melatonin 60 mg/kg + sertraline 10 mg/kg (p < 0,05); on the contrary; agomelatine 25 mg/kg was significantly inferior to this combination in prolonging reaction times (p = 0,041). Melatonin 90 mg/kg but not 60 mg/kg was significantly superior to placebo in prolonging reaction times (p < 0.0001). Both agomelatine 50 mg/kg and 35 mg/kg were superior to agomelatine 25 mg/kg (p < 0.0001 and p = 0.002, respectively), but the difference between agomelatine 50 mg/kg and 35 mg/kg was not significant. Conclusions: We demonstrated that agomelatine is superior to melatonin on pain behavior in a dose -dependent manner using an experimental pain model. The a ddition of a serotonergic agent increased the antinociceptive effect of melatonin in regard to agomelatine, but high doses of agomelatine were still more effective, suggesting a dose -dependent effect of agomelatine on 5-HT2c receptors.