Antagonism of alpha-adrenoceptor agonist-induced antinociception in the rat.

The present study investigated the effects of WB4101, a selective alpha 1-adrenoceptor blocking agent, and idazoxan, a selective alpha 2-adrenoceptor blocking agent, on antinociception and sedation in the rat mediated by adrenoceptors. Selective alpha 1-adrenoceptor agonists, e.g. ST587 and methoxamine induced antinociception but only elicited slight sedation; their antinociceptive effects were antagonized by WB4101 but not by idazoxan. In contrast, the marked sedative and antinociceptive effects induced by the selective alpha 2-adrenoceptor agonist, UK 14,304, were attenuated by idazoxan, but were little affected by WB4101. The mixed alpha 1/alpha 2-adrenoceptor agonists, clonidine and ICI 106,270, had differing profiles with respect to their antagonist interactions; the antinociceptive and sedative effects induced by clonidine were antagonized by idazoxan, whereas the antinociceptive effects of ICI 106,270 were antagonized by WB4101. The slight sedative effects induced by ICI 106,270 were not attenuated by either WB4101 or idazoxan; therefore, these studies give no insight into the mechanism of action for sedation induced by ICI 106,270. These data suggest that antinociception may be mediated by either alpha 1 or alpha 2-adrenoceptors; whereas sedation is predominantly alpha 2-adrenoceptor mediated.