Comparison of the effects of clonidine and yohimbine on pupillary diameter at different illumination levels

Aims To evaluate the pupillary effects of single doses of the alpha(2)-adrenoceptor agonist clonidine and the alpha(2)-adrenoceptor antagonist yohimbine under several illumination conditions. Methods Sixteen healthy male volunteers received clonidine 0.2 mg, yohimbine 22 mg, clonidine 0.2 mg + yohimbine 22 mg in a double-blind placebo-controlled, cross-over study. 2 h post drug ingestion pupil diameter was recorded in darkness, and at luminance levels of 6 Cd m(-2), 91 Cd m(-2) and 360 Cd m(-2). The effects of the active treatments on pupil diameter were also expressed as the differences from the placebo condition ('placebo-corrected' data; mean [95% CI]). Results Clonidine had little effect on pupil diameter in darkness; however, it caused a significant, light-dependent, miosis when the eye was illuminated. On the other hand yohimbine increased pupil size; this increase was significant at 91 and 360 Cd m(-2). There were no significant differences between the effects of the combined treatment (clonidine 0.2 mg + yohimbine 22 mg) and the effect of placebo. Conclusions The pupillary effects of clonidine and yohimbine are likely to reflect the interaction of these drugs with inhibitory alpha(2)-adrenoceptors located on central noradrenergic neurones, which in turn would lead to a decrease and an increase, respectively, in sympathetic outflow to the iris. The light dependence of the pupillary effects of these drugs, however, suggests that the parasympathetic light reflex pathway is also involved, which is known to be under inhibitory control from the central noradrenergic neurones. Modulation of parasympathetic outflow seems to play an important role since both drugs had relatively little effect on pupil diameter in darkness when sympathetic activity predominates.