Antinociceptive effects and spinal cord tissue concentrations after intrathecal injection of guanfacine or clonidine into rats.

In the present study, the antinociceptive effects of intrathecal injections of the alpha 2-adrenoceptor agonists clonidine and guanfacine in rats was determined to establish their dose-response curves. Spinal cord tissue concentrations were also determined in a separate group of animals. Guanfacine was found to be more potent than clonidine and had a considerably longer duration of action. Thus, whereas the analgesic effect of clonidine declined to baseline by 4 hr after injecting doses of up to 50 micrograms, guanfacine still showed a considerable effect 18 hr after injecting both 25 and 50 micrograms. With both compounds, concentration gradients existed within the spinal cord. In the experiments with guanfacine, the region in the spinal cord tissue with the highest concentrations 10 min after injection contained around 30 pmol/mg wet weight. At 3 hr, this figure was around 20 pmol/mg. With clonidine, on the other hand, the concentration decreased from the maximal level of 200 pmol/mg at 10 min to 10 pmol/mg at 3 hr. On all occasions, except 10 min after injecting clonidine, it was found that the maximal tissue concentrations for both drugs remained below the cervical spinal cord, i.e., the rostral spread was less than expected, especially with drugs with such a long duration of action. The present investigation demonstrates analgesic effects of both clonidine and guanfacine after intrathecal administration, with guanfacine proving more potent and longer acting; the difference in duration of action is probably attributable to differences in rates of elimination of the drugs from spinal cord tissue.