July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
NCX 1741, a novel NO-donating derivative of the phosphodiesterase-5 inhibitor avanafil, reduces IOP in models of ocular hypertension and glaucoma
Author Affiliations & Notes
  • Francesco Impagnatiello
    Nicox Research Institute, Bresso, Milan, Italy
  • Elena Bastia
    Nicox Research Institute, Bresso, Milan, Italy
  • Carol B Toris
    University of Nebraska Medical Center, Omaha, Nebraska, United States
    Case Western Reserve University, Cleveland, Ohio, United States
  • Shan Fan
    University of Nebraska Medical Center, Omaha, Nebraska, United States
  • Stefania Brambilla
    Nicox Research Institute, Bresso, Milan, Italy
  • Corinna Galli
    Nicox Research Institute, Bresso, Milan, Italy
  • Nicoletta Almirante
    Nicox Research Institute, Bresso, Milan, Italy
  • Michael V W Bergamini
    Nicox Ophthalmics, Inc., Fort Worth, Texas, United States
    Nicox Ophthalmics, Inc.,, North Carolina, United States
  • Footnotes
    Commercial Relationships   Francesco Impagnatiello, Nicox (E); Elena Bastia, Nicox (E); Carol Toris, Nicox (F); Shan Fan, None; Stefania Brambilla, Nicox (E); Corinna Galli, Nicox (E); Nicoletta Almirante, Nicox (E); Michael Bergamini, Nicox (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 3770. doi:
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      Francesco Impagnatiello, Elena Bastia, Carol B Toris, Shan Fan, Stefania Brambilla, Corinna Galli, Nicoletta Almirante, Michael V W Bergamini; NCX 1741, a novel NO-donating derivative of the phosphodiesterase-5 inhibitor avanafil, reduces IOP in models of ocular hypertension and glaucoma. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3770.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : The nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling pathway plays a major role in aqueous humour drainage and intraocular pressure (IOP) homeostasis. The effects of this signaling pathway are silenced when cGMP is degraded by the phosphodiesterase type-5 enzyme (PDE-5). Here we investigated the IOP-lowering effects of NCX 1741, a novel NO-donating derivative of the PDE-5 inhibitor avanafil in rabbit and non-human primate models of ocular hypertension and glaucoma.

Methods : Ocular normotensive New Zealand White rabbits (ONT-rabbits, n=8) and laser-induced ocular hypertensive non-human primates (OHT-monkeys, n=8) were used. Vehicle (phosphate buffer pH 6.0, Cremophor EL 5%, DMSO 0.3%, BAC 0.02%) or NCX 1741 in the vehicle were instilled (30 μL) in a masked fashion, and IOP was measured by pneumatonometry prior to (baseline) and periodically post-dosing for 5 hours (rabbits) or 24 hours (non-human primates). IOP comparisons were made between vehicle and drug treatments by two-tailed t-tests.

Results : In ONT-rabbits, NCX 1741 (2.2%, 30 μL, n=8) decreased IOP by -2.4 ± 0.7 mmHg (p<0.01) at 60 min compared to vehicle treatment. In ocular OHT-monkeys NCX 1741 progressively lowered IOP over time reaching a maximum effect between 5 and 8 hours post-dosing (IOP changes were -5.3 ± 2 mmHg, p<0.05 and -6.0 ± 2.1 mmHg, p<0.01 compared to vehicle at 5 hours and 8 hours post-dosing, respectively). Interestingly, the IOP-lowering effect of NCX 1741 was still evident, albeit not significantly, at 24 hours after dosing (IOP change = -4.6 ± 2.4 mmHg).

Conclusions : NCX 1741 effectively lowers IOP in ONT-rabbits and OHT-monkeys. Moreover, in OHT-monkeys, the IOP-lowering effects of NCX 1741 appear to persist for 24 hours post-dosing suggesting that NCX 1741 may represent a potent and effective IOP-lowering agent.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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