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phosphodiesterase inhibitor
A phosphodiesterase inhibitor is a drug that blocks one or more of the five subtypes of the enzyme phosphodiesterase (PDE), thereby preventing the inactivation of the intracellular second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) by the respective PDE subtype(s).
==History==
The different forms or subtypes of phosphodiesterase were initially isolated from rat brains by Uzunov and Weiss in 1972〔Uzunov, P. and Weiss, B.: Separation of multiple molecular forms of cyclic adenosine 3',5'-monophosphate phosphodiesterase in rat cerebellum by polyacrylamide gel electrophoresis" ''Biochim. Biophys. Acta'' 284:220-226, 1972. doi:10.1016/0005-2744(72)90060-5.〕 and were soon afterward shown to be selectively inhibited in the brain and in other tissues by a variety of drugs.〔Weiss, B.: Differential activation and inhibition of the multiple forms of cyclic nucleotide phosphodiesterase. ''Adv. Cycl. Nucl. Res.'' 5:195-211, 1975.〕〔Fertel, R. and Weiss, B.: Properties and drug responsiveness of cyclic nucleotide phosphodiesterases of rat lung" ''Mol. Pharmacol'' 12:678-687, 1976.〕 The potential for selective phosphodiesterase inhibitors as therapeutic agents was predicted as early as 1977 by Weiss and Hait.〔Weiss, B. and Hait, W.N.: Selective cyclic nucleotide phosphodiesterase inhibitors as potential therapeutic agents. ''Ann. Rev. Pharmacol. Toxicol.'' 17:441-477, 1977.〕 This prediction meanwhile has proved to be true in a variety of fields.
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