PHARMACOLOGICAL ANALYSIS OF ALPHA-2 ADRENERGIC-MECHANISMS IN NOCICEPTION AND ATAXIA

  • 1 January 1985
    • journal article
    • research article
    • Vol. 232  (3) , 883-889
Abstract
In order to assess the involvement of .alpha.-2-adrenergic receptors in nociception, the in vitro potencies of 7 .alpha.-2 adrenergic agonists (clonidine, guanabenz, guanfacine, BHT-920, ICI 106270, xylazine and iofexidine) were compared with their ability to prevent the writhing response elicited by i.p. administration of phenyl-p-guinone. Administration of each compound elicited antinociception, and this effect was attenuated by pretreatment with the .alpha.-2 adrenergic antagonist, yohimbine. The potency of these compounds to cause antinociception was correlated with their potency to displace [3H]clonidine from its binding site on brain membranes and with their ability to inhibit the twitch of the electrically stimulated vas deferens, suggesting an .alpha.-2 involvement in the antinociceptive action. In addition to causing antinociception, administration of these agonists also impaired rotorod performance in mice. These agonists were 2.5-72 times more potent in inhibiting writhing than in impairing rotorod performance, and, except for ICI 106270, there was a correlation between antinociceptive and ataxic potency. ICI 106270 was a notable exception to this correlation, producing only minimal ataxia, which unlike the other agonists was not reversed by yohimbine. .alpha.-2 adrenergic agonists can produce antinociception and this may be dissociable from the ataxia.