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  • Journal
    Digital Access Ovid v. 1-, 1993-
  • Article
    Smolen VF, Park CS, Williams EJ.
    J Pharm Sci. 1975 Mar;64(3):520-8.
    The augmentation of carbachol miotic activity attributable to enhanced transcorneal absorption, which results from the action of cationic adjuvants included in ophthalmic vehicles, suggested a study of carbachol-corneal tissue interaction as a further step toward understanding the phenomenon. The present study was performed in vivo using an innocuous electrometric technique. A fixed charge density of the corneal epithelial surface versus carbachol concentration profile was obtained from the electrometric results; it revealed three distinct concentration regions defined by precipitous decreases of fixed charge over extremely small concentration ranges. This anomalous behavior is attributed to cooperative alterations in the binding affinities of fixed anionic sites on the tissue surface, which result in an all-or-none release of protons and/or other nicrocations. The unmasked anionic sites become reoccupied with carbachol except in the last region where the reoccupation by carbachol is competitive with other cations in the solution in contact with the surface. This behavior, postulated on the basis of the construction of a carbachol-tissue binding isotherm from which thermodynamic interaction affinities were computed, was corroborated by the observed dependency of the duration of miotic activity on carbachol concentration. Allosteric interactions between anionic binding sites, which are mediated through electron inductive and electrostatic field effects and likely involve a cooperative alteration in tissue water structure, are implicated as underlying the observed phenomena.
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