Antinociceptive activity of clonidine in the mouse, rat and dog

The antinociceptive activities of clonidine have been determined against several qualitatively different noxious stimuli in the mouse, rat and dog. In these tests clonidine given subcutaneously was 6 to 7 times more potent than morphine. Both clonidine and morphine were more potent against responses to pressure and chemical nociceptive stimuli than against responses to heat induced nociception or that induced by electrical tail stimulation. However, unlike morphine the effects of clonidine in these latter tests were only seen at doses that also caused sedation and so these animals were less able to respond to the nociceptive stimuli. In contrast in pressure, chemical and tooth pulp stimulation tests clonidine produced increases in nociceptive thresholds at doses which caused no overt signs of behavioural depression. Comparisons of the relative potencies of clonidine and the less lipophilic analogue 4-hydroxyclonidine given subcutaneously and intracerebroventricularly indicate that clonidine induced antinociception is predominantly centrally mediated. However, a peripheral component may also be present in the inhibition of acetylcholine-induced abdominal constriction in the mouse.