Antinociceptive action of tricyclic antidepressant drugs in the rat.

The antinociceptive effects of controlled release amitriptyline, desipramine, and placebo pellets were studied over 3 weeks using the hot plate method in 45 rats. Animals treated with desipramine at total doses of 50 mg (8 mg/kg/day) and 100 mg (16 mg/kg/day) displayed analgesia for up to 48 hours compared with the matching placebo groups. Amitriptyline did not produce significant analgesia at the same doses. By 72 hours until the final evaluation period at 21 days, the antinociceptive action of desipramine was no longer evident. These results suggest that relatively small continuously released doses of desipramine produce analgesia within 24 hours in this animal model, but an apparent analgesic tolerance develops within 3 days.