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.
MeSH terms
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3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors
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3',5'-Cyclic-GMP Phosphodiesterases / antagonists & inhibitors
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Animals
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Asthma / drug therapy
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Asthma / enzymology
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Cyclic Nucleotide Phosphodiesterases, Type 3
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Cyclic Nucleotide Phosphodiesterases, Type 4
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Cyclic Nucleotide Phosphodiesterases, Type 5
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Erectile Dysfunction / drug therapy
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Erectile Dysfunction / enzymology
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Heart Failure / drug therapy
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Heart Failure / enzymology
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Humans
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Inflammation / drug therapy
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Inflammation / enzymology
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Male
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Phosphodiesterase Inhibitors / pharmacology*
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Phosphodiesterase Inhibitors / therapeutic use
Substances
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Phosphodiesterase Inhibitors
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3',5'-Cyclic-AMP Phosphodiesterases
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Cyclic Nucleotide Phosphodiesterases, Type 3
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Cyclic Nucleotide Phosphodiesterases, Type 4
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3',5'-Cyclic-GMP Phosphodiesterases
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Cyclic Nucleotide Phosphodiesterases, Type 5
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PDE5A protein, human