MK-927 : a topically active ocular hypotensive carbonic anhydrase inhibitor
MK-927 (dl-5,6-dihydro-4-(2-methylpropylamino)-4H-thieno(2,3b)thiopyra n-2-sulfonamide-7,7-dioxide hydrochloride) is a water soluble, carbonic anhydrase inhibitor (CAI) possessing a Ki of 12.0 nM against purified human carbonic anhydrase II in vitro. The acute instillation of one drop (50 microliter...
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Veröffentlicht in: | Journal of ocular pharmacology 1990, Vol.6 (1), p.9-22 |
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Sprache: | eng |
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Zusammenfassung: | MK-927 (dl-5,6-dihydro-4-(2-methylpropylamino)-4H-thieno(2,3b)thiopyra n-2-sulfonamide-7,7-dioxide hydrochloride) is a water soluble, carbonic anhydrase inhibitor (CAI) possessing a Ki of 12.0 nM against purified human carbonic anhydrase II in vitro. The acute instillation of one drop (50 microliters) of 0.5%, 1% and 2% solutions of MK-927 maximally decreased the intraocular pressure (IOP) of ocular hypertensive, cynomolgus monkeys by 4.7, 5.9 and 9.6 mm Hg, respectively. The decline of 9.6 mm Hg represented a reduction of 27% from the corresponding vehicle-treated value of 35.3 mm Hg. Peak reductions in IOP were present at 2 to 4 hr after the instillation of the three doses and the ocular hypotensive effect was waning at 6 hr. The IOP of normotensive, monkey eyes was significantly lowered by 1% and 2% solutions of MK-927 with the effect being more transient in these eyes than in hypertensive eyes. The elevated IOP of alpha-chymotrypsinized rabbits was dose-dependently decreased by 0.01%, 0.1% and 0.5% solutions of MK-927. MK-927 modestly bound to rabbit ocular pigment in vitro and the concentrations of MK-927 in the iris + ciliary body of pigmented rabbits were higher than those in the same tissue of albino rabbits after dosing with 0.5% MK-927. The ocular hypotensive effect of 2% MK-927 was greater in magnitude and longer in duration in normal pigmented than in albino rabbits. The IOP lowering action of MK-927 was local as evidenced by results of ocular distribution studies and the observation that the unilateral instillation of 0.5% MK-927 into the contralateral eye was devoid of effect on the untreated, hypertensive eye of alpha-chymotrypsinized rabbits. MK-927 has been selected for topical evaluation in glaucoma patients. |
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ISSN: | 8756-3320 1080-7683 1557-7732 |
DOI: | 10.1089/jop.1990.6.9 |