Prostaglandin subtype-selective and non-selective IOP-lowering comparison in monkeys.

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Citation

Gabelt BT, Hennes EA, Bendel MA, Constant CE, Okka M, Kaufman PL

Prostaglandin subtype-selective and non-selective IOP-lowering comparison in monkeys.

J Ocul Pharmacol Ther. 2009 Feb;25(1):1-8. doi: 10.1089/jop.2008.0089.

PubMed ID
19232013 [ View in PubMed
]
Abstract

The aim of this study was to determine whether the magnitude of the intraocular-pressure (IOP)-lowering response in monkeys to the nonselective prostaglandin (PG)F(2a)-isopropyl ester (ie) can be reproduced by combining other PG-subtype-selective compounds. IOP was lowered by approximately 25% after 4-5 days of topical administration with latanoprost (FP agonist, 1.5 microg, q.d.), bimatoprost (prostamide, whose metabolites have been shown to be FP agonists; 9 microg, q.d.), or travoprost (FP agonist, 1.2 microg, q.d) or the EP2 agonist, butaprost (25 microg, b.i.d.). The EP1 agonist, 17-phenyl trinor (PhT) PGE2 (b.i.d.), and EP3 agonist, sulprostone (b.i.d.), had no IOP-lowering effects. The addition of butaprost, sulprostone (10 microg), or 17PhTPGE2 (25 microg) to latanoprost did not lower IOP more than latanoprost alone. However, treatment with the combination of latanoprost, 17PhTPGE2, butaprost, and sulprostone produced a similar 50-55% reduction in IOP, as did PGF(2)alpha-ie (b.i.d.). In conclusion, latanoprost, travoprost, and bimatoprost produce similar IOP-lowering responses in normotensive monkeys and are most efficacious when administered q.d. pm, compared to b.i.d. The combination of the FP, EP1, EP2, and EP3 agonists used in this study was sufficient to lower IOP by the same magnitude as PGF(2)alpha-ie, suggesting that combining PG-subtype agonists may be a potent antiglaucoma strategy.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
BimatoprostProstaglandin E2 receptor EP3 subtypeProteinHumans
Yes
Agonist
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