Comparison of the effects of moclobemide and selegiline on tyramine-evoked mydriasis in man.
OBJECTIVE
To examine the feasibility of using the human iris in vivo for the assessment of the interaction between tyramine and monoamine oxidase (MAO) inhibitors. To examine the relative roles of the two forms of MAO in terminating the response to sympathomimetic amines in the iris, by comparing the effects of single oral doses of moclobemide, a selective MAO-A inhibitor, and selegiline, a selective MAO-B inhibitor, on mydriatic responses to tyramine.


METHODS
Twelve healthy male volunteers participated in three monthly sessions, each associated with ingestion of one capsule (moclobemide 450 mg, selegiline 10 mg, or placebo), according to a double-blind, balanced, cross-over design. Tyramine hydrochloride eye-drops (75 mM, 2 x 10 microl) were instilled three times in the left conjuctival sac at 40 min intervals. Pupil diameter was monitored with a binocular infrared television pupillometer before and for 4.5 h after ingestion of the capsule. The pupillary response to tyramine was expressed as the area under the pupil diameter x time curve (arbitrary units). A blood sample was taken before and 2 h after ingestion of the capsule, for the assay of platelet MAO-B activity, and plasma 3,4-dihydroxyphenylglycol (DHPG) concentration, an index of MAO-A activity. Platelet MAO activity was assayed radiochemically, using [14C]-phenylethylamine as substrate, and plasma DHPG by high performance liquid chromatography (h.p.l.c.). The results were analysed using analysis of variance with repeated measures, followed by Bonferroni's corrected t-test, using a significance criterion of P < 0.05.


RESULTS
Both moclobemide and selegiline, compared with placebo, caused significant miosis 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 response to tyramine was potentiated by moclobemide, compared with the response recorded in the presence of placebo. The responses to tyramine (arbitrary units +/- s.e. mean) were: placebo 77.08 +/- 11.65, moclobemide 140.25 +/- 18.9, selegiline 72.75 +/- 12.35. Both moclobemide and selegiline significantly reduced platelet MAO activity, compared with placebo. 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, moclobemide -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 pretreatment level were: placebo -0.01 +/- 0.24, moclobemide -4.98 +/- 0.32, selegiline -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 sympathetic nerve terminals. The lack of effect of selegiline on tyramine-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 agreement with previous reports and consistent with the relative selectivity 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 sympatholytic action of the drugs.
Bitsios
P
P
Department of Psychiatry, University of Nottingham, UK.
Langley
R W
RW
Tavernor
S
S
Pyykkö
K
K
Scheinin
M
M
Szabadi
E
E
Bradshaw
C M
CM
D000328:Adult; D000704:Analysis of Variance; D001549:Benzamides / Q000008:administration & dosage / Q000494:pharmacology*; D001792:Blood Platelets / Q000378:metabolism; D004311:Double-Blind Method; D004347:Drug Interactions; D005240:Feasibility Studies; D006801:Humans; D008297:Male; D008540:Meiosis / Q000187:drug effects; D020912:Moclobemide; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D009284:Naphthols / Q000097:blood; D011409:Propylene Glycols / Q000097:blood; D011680:Pupil / Q000187:drug effects* / Q000502:physiology; D012642:Selegiline / Q000008:administration & dosage / Q000494:pharmacology*; D014439:Tyramine / Q000494:pharmacology*
D001549:Benzamides; D008996:Monoamine Oxidase Inhibitors; D009284:Naphthols; D011409:Propylene Glycols; C056310:1-((3-hydroxy-4-methoxy)-1-naphthoxy)-2,3-propanediol; D012642:Selegiline; D008995:Monoamine Oxidase; D020912:Moclobemide; D014439:Tyramine