Antinociceptive effects of tricyclic antidepressants and their noradrenergic metabolites

This study evaluates the antinociceptive effect of several tricyclic antidepressants in four nociceptive tests which employ either thermal (hot plate and tail flick tests) or chemical (formalin and acetic acid tests) stimuli. Forced swimming test was also performed as a model of depression and an activity test was also performed. Mixed antidepressants in current clinical use: amitriptyline, imipramine and clorimipramine and their respective main secondary metabolites which preferentially inhibit noradrenaline reuptake: nortriptyline, desipramine and desmethylclorimipramine, were tested (2.5–20 mg/kg, i.p.) in mice. The results show a stronger antinociceptive effect in chemical tests induced by all the drugs, compared with thermal tests. The doses needed to produce antinociception were lower than those inducing an antidepressive effect, both effects being mutually independent. The overall results show that preferentially noradrenergic tricyclics induced an antinociceptive effect comparable with that of mixed tricyclics, indicating that noradrenaline reuptake plays an important role in tricyclic-induced antinociception.