Antagonism of clonidine antinociception by buspirone and 1-(2-pyrimidinyl)-piperazine.

The effects of pretreatment with buspirone and its major metabolite 1-(2-pyrimidinyl)-piperazine (1-PP) on antinociception produced by clonidine were investigated in mice. Buspirone and 1-PP dose dependently attenuated the antinociceptive action of s.c. administered clonidine in the writhing and tail-flick assays. In both assays, 1-PP was more potent than buspirone in antagonizing clonidine-induced antinociception. After s.c. pretreatment with buspirone (8 mg/kg) and 1-PP (4 mg/kg), the antinociceptive ED50 values of s.c. clonidine were significantly increased. The antagonistic effects of buspirone and 1-PP on clonidine-induced antinociception may be due to their alpha 2-adrenoceptor antagonist activity.