Interactions between guanabenz and clonidine in their antinociceptive effects in the rat

Based on the hot-plate algesiometric assay in conscious Sprague-Dawley rats, we observed that both guanabenz and clonidine, at a subcutaneous dose of 5 and 1 mg/kg, respectively, exhibited significant antinociceptive potencies. Paradoxical actions on the hot-plate responses, however, were exerted by guanabenz at lower doses, varying from hyperalgesia (1 mg/kg) to no effect (2 mg/kg). A pretreatment of clonidine (1 mg/kg) substantially potentiated the antinociceptive efficacy of the two latter doses, but failed to further augment the pain-suppressive action of guanabenz at 5 mg/kg. These interactive effects of the two alpha-adrenoceptor agonists suggest that they may share a common mechanism(s) in their analgesic actions.