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 human circular ciliary muscle obtained within 24 h of postmortem hypoxia was 517 nmol/l and 135 mg, respectively. These values for carbachol did not differ significantly from that of the longitudinal ciliary muscle. However, when tested at 1 mumol/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 > carbachol, 1/4 > pilocarpine, 1/19 > aceclidine, 1/132. The relative order of potency of agonists was similar for the longitudinal muscle. Only pilocarpine and aceclidine were partial agonists which produced 80-85% of the maximum response. When compared with the EC50 values of aceclidine 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 are discussed. The pKB values of muscarinic antagonists on the circular ciliary muscle were: atropine, 8.8; cyclopentolate, 7.8; tropicamide, 7.4; P.F. HHSiD, 7.0; pirenzepine, 6.4; and methoctramine, 5.7. Nearly equal pKB values of each antagonist were obtained for the longitudinal ciliary muscle and iris sphincter. Based on the affinity constants of various competitive antagonists, the human iris as well as ciliary muscles may contain M3, M2 or M4 subtypes of muscarinic receptors.
Department of Ophthalmology, Kitasato University, School of Medicine, Kanagawa, Japan.
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Ishikawa
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DeSantis
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Patil
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002924:Ciliary Body / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D007498:Iris / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D018721:Muscarinic Agonists / Q000494:pharmacology*; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D011976:Receptors, Muscarinic / Q000378:metabolism
D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic