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

Abstract

Aims To evaluate the pupillary effects of single doses of the a 2 -adrenoceptor agonist clonidine and the a 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 x2 , 91 Cd m x2 and 360 Cd m x2 . 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 signi®cant, light-dependent, miosis when the eye was illuminated. On the other hand yohimbine increased pupil size; this increase was signi®cant at 91 and 360 Cd m x2 . There were no signi®cant 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 re¯ect the interaction of these drugs with inhibitory a 2 -adrenoceptors located on central noradrenergic neurones, which in turn would lead to a decrease and an increase, respectively, in sympathetic out¯ow to the iris. The light dependence of the pupillary effects of these drugs, however, suggests that the parasympathetic light re¯ex pathway is also involved, which is known to be under inhibitory control from the central noradrenergic neurones. Modulation of parasympathetic out¯ow seems to play an important role since both drugs had relatively little effect on pupil diameter in darkness when sympathetic activity predominates.

Arousal and the pupil: why diazepam-induced sedation is not accompanied by miosis

“…As reported previously (Bitsios et al 1998;Phillips et al 2000b;Hou et al 2005;Samuels et al 2006a), there was a near-linear negative relationship between the logarithm of the level of ambient luminance and resting pupil diameter. The luminance level/pupil diameter curves were displaced upwards (pupil dilatation) by tropicamide and downwards (pupil constriction) by dapiprazole.…”

“…Measurements were carried out in a light-sealed darkened room. Pupil diameter was first recorded in darkness and then under each of the increasing luminance levels for 2 s at 4 Hz and stored to disk for off-line analysis (Phillips et al 2000b). Measurements were repeated four times at each level of luminance, and mean of the four measurements was used for future analysis.…”

Relationship between sedation and pupillary function: comparison of diazepam and diphenhydramine

“…Measurements were carried out in a darkened room. Pupil diameter was first recorded in darkness and then under each of the increasing luminance levels for 2 s at 4 Hz and stored to disk for off-line analysis [26].Light reflex response was measured by an infrared binocular television pupillometer (TVC 1015B; Applied Science Laboratories, Waltham, MA, USA). The method used here was similar to that used by Bitsios et al [6,18,27].…”

“…Measurements were carried out in a darkened room. Pupil diameter was first recorded in darkness and then under each of the increasing luminance levels for 2 s at 4 Hz and stored to disk for off-line analysis [26].…”

Lack of sedative effects after vespertine intake of oxazepam as hypnotic in healthy volunteers

“…Phillips investigated differences in sedative effects of three antidepressants by means of PUI (Phillips et al 2000a). They tested a selective noradrenalin re-uptake inhibitor, reboxetine, a selective serotonin re-uptake inhibitor, fluvoxamine, a tricyclic antidepressant, amitriptyline and a placebo.…”