摘要:

L-671,152 is a water-soluble, carbonic anhydrase inhibitor structurally similar to MK-927, a carbonic anhydrase inhibitor that, on topical administration, lowers the intraocular pressure (IOP) of experimental animals and humans. L-671,152 was more potent than MK-927 at inhibiting purified, human erythrocyte carbonic anhydrase IIin vitro, as reflected in their respective IC50values of 0.16 nM and 1.19 nM. Both compounds were compared for topical, ocular hypotensive activity in pigmented rabbits and cynomolgus monkeys. Ocular hypertension was induced in the latter by argon laser photocoagulation of the trabecular meshwork. A 2% solution of L-671,152 was more potent than 2% MK-927 in lowering the IOP of ocular hypertensive monkeys, the maximum reductions being 13.8 mm Hg (37%) and 9.6 mm Hg (27%) at 5 hr and 4 hr, respectively. Moreover, the duration of action of L-671,152 was superior to that of MK-927. The ocular hypotensive effect of L-671,152 was greater than that of MK-927 over a range of concentrations (0.5% - 2%) in pigmented rabbits whose IOP was inherently elevated. The peak declines in the IOP of these rabbits after the instillation of 2% solutions of L-671,152 and MK-927 were 6.1 mm Hg and 4.8 mm Hg, respectively. L-671,152 was very effective in lowering the elevated IOP ofα-chymotrypsinized rabbits and the unilateral instillation of 0.5% L-671,152 into the contralateral eye failed to decrease the elevated IOP of theα-chymotrypsinized eye. This finding indicates that the site of action of topically applied L-671,152 is local. The enhancement in the potency of L-671,152 over MK-927 is attributed to a greater inhibition of carbonic anhydrase activity.

ISSN:0271-3683    

DOI:10.3109/02713689008999600

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

The transepithelial potential (TEP) and short circuit current (SCC) of the bovine retina pigment epithelium (RPE) were monitored throughout a 3hr period. Application of retinaderived factors to the apical side of the preparation resulted in a stabilization of the TEP and SCC, followed by a secondary rise in both electrical parameters. The late, secondary rise could be eliminated or reduced by the administration of cycloheximide suggesting a dependence upon protein synthesis. The active component(s) is not heat labile and has an apparent molecular weight between 1,000–10,000.After 3 hr of incubation, both control and factor-treated RPE had normal appearing nuclei and mitochondria; however, the factor-treated preparations were significantly thicker (apical to basal membrane) and had more apical processes than the control tissues.

ISSN:0271-3683    

DOI:10.3109/02713689008999601

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

Neural mechanisms of visual perception, Proceedings of the Retina Research Foundation Symposia, Volume Two, edited by D. Man-Kit Lam and C.D. Gilbert, published by the Gulf publishing company, Houston, TX, 1989.Ophthalmalogy: What Shall i do?, edited by J.J. Kanski and B. Daily, published by Butterworth and Co., London, UK, 1989

ISSN:0271-3683    

DOI:10.3109/02713689008999602

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor