Comparison of the effects of clonidine on tyramine- and methoxamine-evoked mydriasis in man.

1. It has been reported previously that clonidine can potentiate tyramine-evoked mydriasis on the pain-free side of cluster headache patients. We examined whether a single oral dose of clonidine (200 micrograms) can also potentiate tyramine-evoked mydriasis in healthy subjects, using mydriasis to methoxamine, a directly acting sympathomimetic amine, as a control. 2. Eight healthy male volunteers participated in four weekly sessions. In the first two sessions (Experiment 1) the effect of clonidine or placebo on the mydriasis to tyramine hydrochloride eyedrops (75 mM; 2 x 10 microliters), and in the last two sessions (Experiment 2) the effect of clonidine or placebo on the mydriasis to methoxamine hydrochloride eyedrops (20 mM; 2 x 10 microliters) was examined. In both experiments subjects were allocated to drugs and sessions according to a double-blind balanced design. In both experiments, pupil diameter of both the treated and the untreated eyes was recorded in standard ambient light and in the dark, before, and 2 h after clonidine/placebo, via binocular infrared television pupillometry. Salivation (dental roll technique), systolic and diastolic blood pressure (sitting), heart rate, and self-ratings of mood and feelings (visual analogue scales), were also measured before, and 2 h after the ingestion of clonidine or placebo. 3. Both tyramine and methoxamine produced a significant mydriasis, which was more prominent in the light condition (change in resting pupil size; mm +/- s.e.mean: tyramine/light 1.05 +/- 0.28; tyramine/dark: 0.73 +/- 0.15; methoxamine/light: 1.65 +/- 0.28; methoxamine/dark: 0.85 +/- 0.15). Clonidine produced a significant miosis in the untreated eye which was more prominent in the light condition (change in resting pupil size; mm +/- s.e.mean: Experiment 1, light: -1.34 +/- 0.19; Experiment 1, dark: -0.46 +/- 0.1; Experiment 2, light -0.97 +/- 0.18; Experiment 2, dark: -0.29 +/- 0.17). Clonidine had no significant effect on either tyramine- or methoxamine-evoked mydriasis. 4. In agreement with previous reports, clonidine significantly reduced salivation (g, mean +/- s.e.mean; Experiment 1: -0.84 +/- 0.22; Experiment 2: -0.55 +/- 0.11), systolic blood pressure (mm Hg; Experiment 1: -17.5 +/- 3.76; Experiment 2: -23.38 +/- 4.67), diastolic blood pressure (mm Hg; Experiment 2: -12.38 +/- 2.05), alertness (mm; Experiment 2: -24.19 +/- 5.40), and anxiety (mm; Experiment 1: -13.82 +/- 4.60), indicating the presence of pharmacodynamically effective tissue levels of the drug. 5. These results show that a single oral dose (200 micrograms) of clonidine causes significant miosis in human subjects, and fails to potentiate tyramine-evoked mydriasis. This indicates that the pupil on the asymptomatic side of cluster headache patients is affected differently from the pupils of healthy volunteers by tyramine and/or clonidine.