title: IOP-Lowering Effect of ONO-9054, A Novel Dual Agonist of Prostanoid EP3 and FP Receptors, in Monkeys.
abstract: OBJECTIVE
  The purpose of this study was to determine whether a better IOP reduction can be observed in conscious, normotensive monkeys treated with ONO-9054, a novel dual EP3 and FP receptor agonist, compared with prostaglandin F2α analogs.
  
  
  METHODS
  The binding affinities and agonistic activities of ONO-AG-367, a carboxylic acid of ONO-9054, to prostanoid receptors were assessed. The IOP-lowering effect of ONO-9054 in monkeys was analyzed after a single (0.3, 3, or 30 μg/mL) or 7-day repeated (30 μg/mL, every day) topical ocular administration. Ophthalmologic and histopathologic evaluations of the eye were performed after 4-week ocular administration of ONO-9054 (30 μg/mL, twice a day) in monkeys.
  
  
  RESULTS
  The ONO-AG-367 exhibited high affinity for both EP3 and FP receptors and potent agonist activity, with EC50 values of 28.6 nM for the EP3 receptor and 22.3 nM for the FP receptor. Single and repeated topical ocular administration of ONO-9054 caused IOP reductions in normotensive monkeys. The maximum IOP reductions on day 7 observed with ONO-9054 (7.3 ± 0.8 mm Hg) were significantly greater than those observed with latanoprost (50 μg/mL, 4.9 ± 0.4 mm Hg) or travoprost (40 μg/mL, 5.1 ± 0.6 mm Hg). In ophthalmologic and histopathologic evaluations, slight and transient mydriasis was occasionally observed and no histopathologic lesions attributable to ONO-9054 were noted.
  
  
  CONCLUSIONS
  A more profound and longer-lasting reduction in IOP in normotensive monkeys can be observed with ONO-9054, which simultaneously stimulates both EP3 and FP receptors, compared with prostaglandin analogs.
authors: Shinsaku
authors: S
authors: Yamane
authors: Tomohiro
authors: T
authors: Karakawa
authors: Satoshi
authors: S
authors: Nakayama
authors: Kazufumi
authors: K
authors: Nagai
authors: Kazumi
authors: K
authors: Moriyuki
authors: Shinichi
authors: S
authors: Neki
authors: Fumitaka
authors: F
authors: Suto
authors: Tohru
authors: T
authors: Kambe
authors: Yasushi
authors: Y
authors: Hirota
authors: Kazuhito
authors: K
authors: Kawabata
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage; D015237:Dinoprost; D004195:Disease Models, Animal; D005500:Follow-Up Studies; D007429:Intraocular Pressure / Q000187:drug effects* / Q000502:physiology; D000077338:Latanoprost; D008252:Macaca fascicularis; D015814:Ocular Hypotension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009883:Ophthalmic Solutions / Q000008:administration & dosage; D011461:Prostaglandins F, Synthetic / Q000008:administration & dosage*; D011982:Receptors, Prostaglandin / Q000819:agonists* / Q000378:metabolism; D058308:Receptors, Prostaglandin E, EP3 Subtype / Q000819:agonists* / Q000378:metabolism
chemical_list: D000959:Antihypertensive Agents; D009883:Ophthalmic Solutions; D011461:Prostaglandins F, Synthetic; D011982:Receptors, Prostaglandin; D058308:Receptors, Prostaglandin E, EP3 Subtype; C034671:prostaglandin F2alpha receptor; D000077338:Latanoprost; D015237:Dinoprost