title: Preclinical efficacy of travoprost, a potent and selective FP prostaglandin receptor agonist.
abstract: Travoprost is the isopropyl ester prodrug of a high affinity, selective FP prostaglandin full receptor agonist. In contrast to travoprost acid's high affinity and efficacy at the FP receptor, there is only sub-micromolar affinity for the DP, EP1, EP3, EP4, IP, and TP receptors. Travoprost produced a lower incidence of ocular irritation than PGF20 isopropyl ester at a dose of 1 microg in the New Zealand albino (NZA) rabbit. Topical ocular application of travoprost produced a marked miotic effect in cats following doses of 0.01, 0.03 and 0.1 microg. In the ocular hypertensive monkey, b.i.d. application of 0.1 and 0.3 microg of travoprost afforded peak reduction in intraocular pressure (IOP) of 22.7% and 28.6%, respectively. Topical application of travoprost was well tolerated in rabbits, cats and monkeys, causing no ocular irritation or discomfort at doses up to 1 microg. Travoprost is a promising ocular hypotensive prostaglandin FP derivative that has the ocular hypotensive efficacy of PGF2alpha isopropyl ester but with less severe ocular side effects.
authors.affiliation: Department of Medicinal Chemistry, Glaucoma Research, Alcon Research Ltd., Fort Worth, TX 76134, USA. Mark.Hellberg@AlconLabs.com
authors.forename: M R
authors.initials: MR
authors.lastname: Hellberg
authors.forename: V L
authors.initials: VL
authors.lastname: Sallee
authors.forename: M A
authors.initials: MA
authors.lastname: McLaughlin
authors.forename: N A
authors.initials: NA
authors.lastname: Sharif
authors.forename: L
authors.initials: L
authors.lastname: Desantis
authors.forename: T R
authors.initials: TR
authors.lastname: Dean
authors.forename: P W
authors.initials: PW
authors.lastname: Zinke
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000287:Administration, Topical; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002415:Cats; D002417:Cattle; D003008:Cloprostenol / Q000031:analogs & derivatives / Q000494:pharmacology*; D003338:Corpus Luteum / Q000378:metabolism; D015237:Dinoprost / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D008251:Macaca; D051379:Mice; D009798:Ocular Hypertension / Q000188:drug therapy; D009883:Ophthalmic Solutions; D010716:Phosphatidylinositols / Q000378:metabolism; D011817:Rabbits; D011982:Receptors, Prostaglandin / Q000819:agonists*; D014129:Trabecular Meshwork / Q000187:drug effects; D000069557:Travoprost
chemical_list: D000959:Antihypertensive Agents; D009883:Ophthalmic Solutions; D010716:Phosphatidylinositols; D011982:Receptors, Prostaglandin; C034671:prostaglandin F2alpha receptor; D003008:Cloprostenol; D015237:Dinoprost; D000262:Adenylyl Cyclases; D000069557:Travoprost