In the study two potassium channel activators, cromakalim and nicorandil, were investigated in rabbits using three different levels of intraocular pressures (IOPs), including alpha-chymotrypsin-induced ocular hypertension, hypotension (IOP recovery method) and normal tension. Cromakalim significantly increased IOP during the initial period in normotensive and hypotensive rabbits, but in the later time, reduced IOP in the alpha-chymotrypsin-induced model. Nicorandil had a similar but less potent effect. In addition, cromakalim also affected ocular blood flows, which had a trend to reduce blood flow about 2-3 hr later, after topical administration of the eyedrop. Two possible mechanisms for increasing IOP effect of potassium channel activators were: (a) enhancing the formation of aqueous humor; (b) relaxing the trabecular meshwork to reduce the outflow of aqueous humor.

A series of thiadiazole derivatives were topically applied in gels or suspensions to rabbits to determine their ocular hypotensive effect. As a result, the compounds with higher corneal permeabilities showed stronger effect in lowering IOP. In addition, gels also caused stronger effect than suspensions. Different concentrations of gel preparations produced diverse ocular hypotensive effects. A linear relationship between the integrated IOP response and logarithm concentration of inhibitor was found. It is proposed that the ocular hypotensive effect was attributed to the level of inhibitor in ciliary body.