Inhibition of aceclidine-stimulated outflow facility, accommodation and miosis in rhesus monkeys by muscarinic receptor subtype antagonists.
Aceclidine can dissociate accommodative and outflow facility responses in monkeys and humans. We sought to determine if different muscarinic receptor subtypes control outflow facility, accommodative and pupillary responses to aceclidine in the living rhesus monkey eye, as a possible basis for this separation. Each eye was cannulated with one branched and one unbranched needle. Baseline measurements (of outflow facility by two-level constant pressure perfusion; refraction by Hartinger coincidence refractometry and pupil diameter by vernier calipers) were recorded after anterior chamber exchange with (one eye) or without (opposite eye), muscarinic receptor subtype antagonist (pirenzepine, AF-DX 116 or 4-DAMP). The eyes were then exchanged a second time with these solutions plus added aceclidine. The response to aceclidine (the differences from baseline) in the presence or absence of antagonist were compared. The M3 muscarinic receptor subtype antagonist 4-DAMP was the most potent inhibitor of all three responses to aceclidine. The dissociation of accommodative, outflow facility and miotic responses to aceclidine in rhesus monkeys does not appear to be due to differences in the muscarinic receptor subtypes that can currently be distinguished pharmacologically.
Gabelt
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Department of Ophthalmology, University of Wisconsin, Madison.
Kaufman
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D000065:Accommodation, Ocular / Q000187:drug effects*; D000818:Animals; D001082:Aqueous Humor / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D008253:Macaca mulatta; D008297:Male; D018727:Muscarinic Antagonists; D010276:Parasympatholytics / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000494:pharmacology; D011680:Pupil / Q000187:drug effects*; D011812:Quinuclidines / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D018727:Muscarinic Antagonists; D010276:Parasympatholytics; D010880:Piperidines; D011812:Quinuclidines; C084650:aceclidine; D010890:Pirenzepine; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; C048593:otenzepad