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NCX-911, a novel nitric oxide-releasing PDE5 inhibitor relaxes rabbit corpus cavernosum in the absence of endogenous nitric oxide

International Journal of Impotence Research volume 16, pages 195–200 (2004)Cite this article

Abstract

Phosphodiesterase type 5 (PDE5) inhibitors have reduced efficacy in treating erectile dysfunction (ED) in conditions where there is a lack of endogenous nitric oxide (NO). Therefore, NO-releasing PDE5 inhibitors have been developed. Here we report the effect of such a compound, NCX-911, on the tone and nitrergic relaxations of rabbit corpus cavernosum in the absence or presence of a NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 500 μM). NCX-911 was found to be as potent as sildenafil at inducing relaxation of rabbit cavernosum (EC50 values 997.8±195.7 and 1000.5±140.8 nM, respectively). The potency of NCX-911 was not altered, but that of sildenafil decreased five-fold in the presence of L-NAME (EC50 values 1281.2±268.3 and 4959.1±882.1, nM respectively, P<0.001 for sildenafil). Both compounds potentiated nitrergic relaxations with similar potencies. These results suggest that NO-releasing PDE5 inhibitors could potentially be more useful than PDE5 inhibitors in the treatment of ED in conditions where there is a lack of endogenous NO.

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Acknowledgements

This work and JS Kalsi are supported by the St Peter's Andrology Research Fund. JS Kalsi is a recipient of Young Investigator's Award from the International Society for Sexual and Impotence Research (2002). S Cellek is a fellow of the Juvenile Diabetes Research Foundation. We thank D Madge for extracting sildenafil citrate.

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Authors and Affiliations

  1. Institute of Urology and Nephrology, University College London, London, UK

    J S Kalsi, P D Kell & D J Ralph

  2. Wolfson Institute for Biomedical Research, University College London, London, UK

    J S Kalsi & S Cellek

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  1. J S Kalsi
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  2. P D Kell
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  3. S Cellek
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  4. D J Ralph
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Correspondence to S Cellek.

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Kalsi, J., Kell, P., Cellek, S. et al. NCX-911, a novel nitric oxide-releasing PDE5 inhibitor relaxes rabbit corpus cavernosum in the absence of endogenous nitric oxide. Int J Impot Res 16, 195–200 (2004). https://doi.org/10.1038/sj.ijir.3901157

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