COMPARISON OF THE EFFECTS OF CLONIDINE ON TYRAMINE-EVOKED AND METHOXAMINE-EVOKED MYDRIASIS IN MAN

1 It has been reported previously that clonidine can potentiate tyrami ne-evoked mydriasis on the pain-free side of cluster headache patients . We examined whether a single oral dose of clonidine (200 mu g) can a lso potentiate tyramine-evoked mydriasis in healthy subjects, using my driasis to methoxamine, a directly acting sympathomimetic amine, as a control. 2 Eight healthy male volunteers participated in four weekly s essions. In the first two sessions (Experiment 1) the effect of clonid ine or placebo on the mydriasis to tyramine hydrochloride eyedrops (75 mM; 2 x 10 mu l), and in the last two sessions (Experiment 2) the eff ect of clonidine or placebo on the mydriasis to methoxamine hydrochlor ide eyedrops (20 mM; 2 x 10 mu l) was examined. In both experiments su bjects were allocated to drugs and sessions according to a double-blin d balanced design. In both experiments, pupil diameter of both the tre ated and the untreated eyes was recorded in standard ambient light and in the dark, before, and 2 h after clonidine/placebo, via binocular i nfrared television pupillometry. Salivation (dental roll technique), s ystolic and diastolic blood pressure (sitting), heart rate, and self-r atings of mood and feelings (visual analogue scales), were also measur ed 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; m m+/-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). Clonid ine 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 metho xamine-evoked mydriasis. 4 In agreement with previous reports, clonidi ne significantly reduced salivation (g, mean+/-s.e.mean; Experiment 1: -0.84+/-0.22; Experiment 2: -0.55+/-0.11), systolic blood pressure (m m Hg; Experiment 1: -17.5+/-3.76; Experiment 2: -23.38+/-4.67), diasto lic 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 tiss ue levels of the drug. 5 These results show that a single oral dose (2 00 mu g) of clonidine causes significant miosis in human subjects, and fails to potentiate tyramine-evoked mydriasis. This indicates that th e pupil on the asymptomatic side of cluster headache patients is affec ted differently from the pupils of healthy volunteers by tyramine and/ or clonidine.