The
anticholinesterase agent echothiophate iodide (EI) and the
cholinergic agent pilocarpine hydrochloride (
pilocarpine), drugs commonly used in
glaucoma therapy, cause
miosis in rabbits as well as in man. In rabbits the
miotic effect decreases after a few days of treatment, a phenomenon possibly due to a
drug-induced decrease in the number of
muscarinic receptors. However, the
muscarinic pupillary contraction caused by stimulation of the retina with light is intact. In this investigation the
miosis caused by the doses of EI was found to be very resistant to
muscarinic or
nerve blockade but inhibited by the
substance P (SP) analog [D-Arg1,D-Pro2,D-Trp7,9, Leu11]SP, which seems to be a SP/SPLI blocker in the rabbit pupillary sphincter.
Miosis caused by
pilocarpine was partly inhibited by
muscarinic blockade and partly by the SP blocker. In eyes treated with EI topically twice daily for three weeks, SP or the red pepper extract
capsaicin, a releaser of SP-like immunoreactivity (SPLI), had less
miotic effect than in control eyes.
Capsaicin caused more pronounced
miosis in eyes treated with topical
pilocarpine for three weeks than in controls. The radioimmunoassay technique did not reveal a significant change in the amount of SPLI in the retinas or iris-ciliary bodies from EI-treated eyes as compared with the controls. It is concluded that, besides
cholinergic miosis, EI causes non-
muscarinic miosis, probably by release of SP or a related substance and that
pilocarpine may have similar effects.