Ocular hypotensive activity of BOL-303259-X, a nitric oxide donating prostaglandin F2α agonist, in preclinical models

Exp Eye Res. 2011 Sep;93(3):250-5. doi: 10.1016/j.exer.2011.03.001. Epub 2011 Mar 9.


The aim of the study was to investigate the ocular hypotensive activity of a nitric oxide (NO)-donating latanoprost, BOL-303259-X, following topical administration. The effect of BOL-303259-X (also known as NCX 116 and PF-3187207) on intraocular pressure (IOP) was investigated in monkeys with laser-induced ocular hypertension, dogs with naturally-occurring glaucoma and rabbits with saline-induced ocular hypertension. Latanoprost was used as reference drug. NO, downstream effector cGMP, and latanoprost acid were determined in ocular tissues following BOL-303259-X administration as an index of prostaglandin and NO-mediated activities. In primates, a maximum decrease in IOP of 31% and 35% relative to baseline was achieved with BOL-303259-X at doses of 0.036% (9 μg) and 0.12% (36 μg), respectively. In comparison, latanoprost elicited a greater response than vehicle only at 0.1% (30 μg) with a peak effect of 26%. In glaucomatous dogs, IOP decreased from baseline by 44% and 10% following BOL-303259-X (0.036%) and vehicle, respectively. Latanoprost (0.030%) lowered IOP by 27% and vehicle by 9%. Intravitreal injection of hypertonic saline in rabbits increased IOP transiently. Latanoprost did not modulate this response, whereas BOL-303259-X (0.036%) significantly blunted the hypertensive phase. Following BOL-303259-X treatment, latanoprost acid was significantly elevated in rabbit and primate cornea, iris/ciliary body and aqueous humor as was cGMP in aqueous humor. BOL-303259-X lowered IOP more effectively than latanoprost presumably as a consequence of a contribution by NO in addition to its prostaglandin activity. The compound is now in clinical development for the treatment of glaucoma and ocular hypertension.

MeSH terms

  • Administration, Topical
  • Animals
  • Antihypertensive Agents / pharmacokinetics
  • Antihypertensive Agents / pharmacology*
  • Aqueous Humor / enzymology
  • Cell Line
  • Ciliary Body / metabolism
  • Cyclic GMP / metabolism
  • Dinoprost / agonists*
  • Disease Models, Animal*
  • Dogs
  • Drug Evaluation, Preclinical
  • Female
  • Glaucoma / drug therapy*
  • Glaucoma / metabolism
  • Guanylate Cyclase / metabolism
  • Intraocular Pressure / drug effects*
  • Iris / metabolism
  • Latanoprost
  • Macaca fascicularis
  • Male
  • Nitric Oxide / metabolism*
  • Nitric Oxide Donors / pharmacokinetics
  • Nitric Oxide Donors / pharmacology*
  • Ocular Hypertension / drug therapy*
  • Ocular Hypertension / metabolism
  • Prostaglandins F, Synthetic / pharmacokinetics
  • Prostaglandins F, Synthetic / pharmacology*
  • Rabbits
  • Rats
  • Tonometry, Ocular


  • Antihypertensive Agents
  • BOL 303259-X
  • Nitric Oxide Donors
  • Prostaglandins F, Synthetic
  • Nitric Oxide
  • Latanoprost
  • Dinoprost
  • Guanylate Cyclase
  • Cyclic GMP