Ocular effects of antimuscarinic compounds: is clinical effect determined by binding affinity for muscarinic receptors or melanin pigment?
Although antimuscarinic drugs are being used with increasing frequency in clinical practice for the purposes of mydriasis and cycloplegia, the extent of their actions varies considerably between different compounds. Investigation of the binding characteristics of these agents revealed that as their reported clinical potency increased, so did their specific binding affinity for muscarinic receptors in the iris sphincter and ciliary muscle and their nonspecific binding affinity for melanin pigment. However, the affinity of each drug for melanin pigment was much lower than for the muscarinic receptors. Therefore, although binding to melanin can significantly influence the overall response, differences in the clinical effect of various compounds appear to be primarily due to their differences in specific affinity for muscarinic binding sites.
German
E J
EJ
Department of Optometry, University of Bradford, West Yorkshire, United Kingdom.
Wood
D
D
Hurst
M A
MA
D000818:Animals; D001665:Binding Sites; D002924:Ciliary Body / Q000187:drug effects*; D005260:Female; D066298:In Vitro Techniques; D007498:Iris / Q000187:drug effects*; D008543:Melanins / Q000378:metabolism*; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D012756:Sheep
D008543:Melanins; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic