Elsevier

Drug Discovery Today

Volume 5, Issue 8, 1 August 2000, Pages 320-321
Drug Discovery Today

Update
New PDE5 inhibitors: more selective than Viagra?

https://doi.org/10.1016/S1359-6446(00)01535-XGet rights and content

Section snippets

Mechanism of action of sildenafil

Sildenafil (Fig. 1), which was developed by Pfizer (Sandwich, UK) works by inhibiting the phosphodiesterase type 5 (PDE5) enzyme. In the healthy man who does not have difficulty achieving an erection, sexual stimulation leads to the release of nitric oxide within the blood vessels of the penis. A cascade of biochemical events follow, leading to the production of cGMP, and causing vasodilatation and increased blood flow into the corpus cavernosum of the penis which becomes erect. Simultaneously,

New inhibitors of PDE5

Initially, Rotella and coworkers embarked on this project to identify compounds to treat erectile dysfunction because at that time, no such products were on the market. Rotella said, ‘We saw this as an excellent drug discovery opportunity in a market that we thought was capable of giving us the opportunity to improve people’s quality of life.’

Like researchers at Pfizer, the Bristol-Myers Squibb team began their search with a known inhibitor of PDE5 called zaprinast (Fig. 1), which they modified

References (1)

  • D. Rotella

    N-3-substituted imidazoquinazolinones: potent and selective PDE5 inhibitors as potential agents for treatment of erectile dysfunction

    J. Med. Chem.

    (2000)

Cited by (3)

  • Sildenafil citrate: A therapeutic update

    2001, Clinical Therapeutics
View full text