Comparison of the effects of chronic administration of ciclazindol and desipramine on pupillary responses to tyramine, methoxamine and pilocarpine in healthy volunteers.
Twenty-nine healthy volunteers participated in an experiment lasting for 8 weeks: Phase I (2 weeks)--pre-treatment control period; Phase II (4 weeks)--medication with either ciclazindol hydrochloride (50 mg twice daily), or desipramine hydrochloride (50 mg twice daily) or lactose placebo (twice daily) administered in a single-blind fashion; Phase II (2 weeks)--recovery. Experimental sessions took place twice weekly for the photographic assessment of resting pupil diameter, and for the assessment of one of the following pupillary responses: mydriatic response to methoxamine, mydriatic response to tyramine, miotic response to pilocarpine. Resting pupil diameter increased during medication with either ciclazindol or desipramine. Methoxamine-evoked mydriasis and tyramine-evoked mydriasis were antagonized by both ciclazindol and desipramine. Pilocarpine-evoked miosis was potentiated by both ciclazindol and desipramine. The steady-state plasma levels (mean +/- s.e. mean) of the antidepressants were: ciclazindol: 5.90 +/- 0.74 microM; desipramine: 0.60 +/- 0.17 microM. The antagonism of methoxamine-evoked mydriasis is likely to reflect the blockade of postsynaptic alpha 1-adrenoceptors in the iris by the antidepressants, whereas the antagonism of tyramine-evoked mydriasis may reflect both the blockade of uptake of tyramine into presynaptic adrenergic terminals and the blockade of postsynaptic alpha-adrenoceptors. There is no immediate explanation for the potentiation of pilocarpine-evoked miosis by the two antidepressants.
D000293:Adolescent; D000328:Adult; D000929:Antidepressive Agents, Tricyclic / Q000097:blood / Q000494:pharmacology*; D003891:Desipramine / Q000097:blood / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007211:Indoles / Q000097:blood / Q000494:pharmacology*; D008297:Male; D008729:Methoxamine / Q000494:pharmacology*; D010862:Pilocarpine / Q000494:pharmacology*; D011680:Pupil / Q000187:drug effects*; D014439:Tyramine / Q000494:pharmacology*
D000929:Antidepressive Agents, Tricyclic; D007211:Indoles; D010862:Pilocarpine; D008729:Methoxamine; D003891:Desipramine; D014439:Tyramine; C009990:ciclazindol