Phosphodiesterase inhibitors - PubMed (original) (raw)

Review

Phosphodiesterase inhibitors

Victoria Boswell-Smith et al. Br J Pharmacol. 2006 Jan.

Abstract

Phosphodiesterases are a diverse family of enzymes that hydrolyse cyclic nucleotides and thus play a key role in regulating intracellular levels of the second messengers cAMP and cGMP, and hence cell function. Theophylline and papaverine have historically been used therapeutically and are known to be weak inhibitors of PDE, but to what extent this contributed toward their clinical efficacy was poorly defined. However, the discovery of 11 isoenzyme families and our increased understanding of their function at the cell and molecular level provides an impetus for the development of isoenzyme selective inhibitors for the treatment of various diseases. This review focuses on the development of PDE3 inhibitors for congestive heart failure, PDE4 inhibitors for inflammatory airways disease and most successfully, PDE5 inhibitors for erectile dysfunction.

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Figures

Figure 1

Figure 1

Inhibition of cAMP-PDE activity by methylxanthines. cAMP was incubated with purified cAMP-PDE at 30°C for 30 min in the presence of increasing concentrations of methylxanthines. Data redrawn from Butcher & Sutherland (1962).

Figure 2

Figure 2

The PDE5 inhibitor M&B 22,949 (Zaprinast) augmented relaxation of human corpus cavernosum to electrical field stimulation (Hz). Data showing relaxation of human corpus cavernosum in an isolated preparation (a) or the mean±s.e.m. for 11 subjects (b); to different stimulation frequencies in untreated and M&B 22,949 (1–3 m

M

)-treated tissue. Data re-drawn from Raijfer et al. (1992).

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