COMPARISON OF THE EFFECTS OF MOCLOBEMIDE AND SELEGILINE ON TYRAMINE-EVOKED MYDRIASIS IN MAN

Aims To examine the feasibility of using the human iris in vivo for th e assessment of the interaction between tyramine and monoamine oxidase (MAO) inhibitors. To examine the relative roles of the two forms of M AO in terminating the response to sympathomimetic amines in the iris, by comparing the effects of single oral doses of moclobemide, a select ive MAO-A inhibitor, and selegiline, a selective MAO-B inhibitor, on m ydriatic responses to tyramine. Methods Twelve healthy male volunteers participated in three monthly sessions, each associated with ingestio n of one capsule (moclobemide 450 mg, selegiline 10 mg, or placebo), a ccording to a double-blind, balanced, cross-over design. Tyramine hydr ochloride eye-drops (75 mM, 2 x 10 mu l) were instilled three times in the left conjuctival sac at 40 min intervals. Pupil diameter was moni tored with a binocular infrared television pupillometer before and for 4.5 h after ingestion of the capsule. The pupillary response to tyram ine was expressed as the area under the pupil diameter x time curve (a rbitrary units). A blood sample was taken before and 2 h after ingesti on of the capsule, for the assay of platelet MAO-B activity, and plasm a 3,4-dihydroxyphenylglycol (DHPG) concentration, an index of MAO-A ac tivity. Platelet MAO activity was assayed radiochemically, using [C-14 ]-phenylethylamine as substrate, and plasma DHPG by high performance l iquid chromatography (h.p.l.c.). The results were analysed using analy sis of variance with repeated measures, followed by Bonferroni's corre cted t-test, using a significance criterion of P< 0.05. Results Both m oclobemide and selegiline, compared with placebo, caused significant m iosis in the right (untreated) eye. The changes in pupil diameter (mm/-s.e. mean) from the pretreatment measurement were: placebo -0.09+/-0 .07, moclobemide -0.52+/-0.09, selegiline -0.26+/-0.1. The mydriatic r esponse to tyramine was potentiated by moclobemide, compared with the response recorded in the presence of placebo. The responses to tyramin e (arbitrary units+/-s.e. mean) were: placebo 77.08+/-11.65, moclobemi de 140.25+/-18.9, selegiline 72.75+/-12.35. Both moclobemide and seleg iline significantly reduced platelet MAO activity, compared with place bo. The changes in platelet MAO activity (nmol h(-1) mg(-1) protein+/- s.e. mean) from the pretreatment level were: placebo 0.5+/-0.62, moclo bemide -6.7+/-0.66, selegiline -17.7+/-0.87. Moclobemide significantly reduced plasma DHPG concentration, compared with placebo. The changes in plasma DHPG concentration (nmol l(-1)+/-s.e. mean) from the pretre atment level were: placebo -0.01+/-0.24, moclobemide -4.98+/-0.32, sel egiline -0.51+/-0.26. Conclusions The potentiation of tyramine-evoked mydriasis by moclobemide is likely to reflect the inhibition of MAO-A activity in the iris, consistent with the activity of this enzyme in s ympathetic nerve terminals. The lack of effect of selegiline on tyrami ne-evoked mydriasis argues against a role of MAO-B in terminating the effects of sympathomimetic amines in the iris. The effects of the two drugs on platelet MAO activity and plasma DHPG concentration are in ag reement with previous reports and consistent with the relative selecti vity of moclobemide for MAO-A and of selegiline for MAO-B. The miosis caused by the two MAO inhibitors is likely to be due to a central symp atholytic action of the drugs.