PURPOSE.To assess the effects of Rho-associated kinase (ROCK) inhibition on the intraocular penetration of timolol maleate.METHODS. Ex vivo porcine corneal penetration of timolol maleate, sotalol hydrochloride, or brinzolamide incubated with or without Y-27632 was determined in vertical Franz diffusion cells. The effect of ROCK inhibition on the vasodilation of porcine conjunctival vasculature was assessed by scanning electron microscopy (SEM) and immunohistochemical staining with subsequent laser-scanning confocal microscopy (LSCM). Experiments were conducted in New Zealand White (NZW) rabbits to assess the effect of ROCK inhibition on the intraocular distribution of timolol maleate. CONCLUSIONS. ROCK inhibition reduced the intraocular penetration of administered timolol maleate presumably due to increased systemic elimination through the conjunctival vasculature. It is anticipated that care in order and timing of ROCK inhibitor administration will be warranted for those patients who may be on a multiple topical drug regimen for primary open-angle glaucoma. (Invest Ophthalmol Vis Sci.

The steroid Spironolactone acts primarily as an aldosterone antagonist in human and other mammalian models, but it often has antiandrogenic or feminizing side effects. However, when Spironolactone was added to aquarium water containing adult female western mosquitofish (Gambusia affinis) all specimens exhibited growth of a complex, malelike anal fin, the gonopodium, within 21 d. This unexpected androgenic response to an antiandrogen represents the first report of “paradoxical masculinization” in fishes. This finding indicates that Spironolactone may be of value in the culture of commercially important fish species and possibly in the aquarium industry to enhance formation of secondary sexual characteristics in sexually dimorphic species.

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