SELECTIVITY OF MUSCARINIC AGONISTS INCLUDING (+ -)-ACECLIDINE AND ANTIMUSCARINICS ON THE HUMAN INTRAOCULAR MUSCLES/

The average EC50 value and the maximum response of carbachol on the hu man circular ciliary muscle obtained within 24 h of postmortem hypoxia was 517 nmol/l and 135 mg, respectively. These values for carbachol d id not differ significantly from that of the longitudinal ciliary musc le. However, when tested at 1 mu mol/l of carbachol, the peak response of the longitudinal muscle occurred at 59 sec vs 173 sec for that of the circular muscle of 70 year old donors. The relative potency of the muscarinic agonists on the circular muscle was oxotremorine-M, 1 > ca rbachol, 1/4 > pilocarpine, 1/19 > aceclidine, 1/132. The relative ord er of potency of agonists was similar for the longitudinal muscle. Onl y pilocarpine and aceclidine were partial agonists which produced 80-8 5% of the maximum response. When compared with the EC50 values of acec lidine on the iris sphincter and the longitudinal ciliary muscles, the agonist potency was only 1/28 for the latter tissue. Implications of these findings in relation to the use of these agonists in glaucoma ar e discussed. The pK(B) values of muscarinic antagonists on the circula r ciliary muscle were: atropine, 8.8; cyclopentolate, 7.8; tropicamide , 7.4; P.F. HHSiD, 7.0; pirenzepine, 6.4; and methoctramine, 5.7. Near ly equal pK(B) values of each antagonist were obtained for the longitu dinal ciliary muscle and iris sphincter. Based on the affinity constan ts of various competitive antagonists, the human iris as well as cilia ry muscles may contain M-3, M-2 or M-4 subtypes of muscarinic receptor s.