Phosphodiesterase enzyme

Phosphodiesterase enzymes show a distinctive molecular structure 373... 

One of the primary mechanisms for regulation of phosphodiesterase enzyme activity is phosphorylation 374 Phosphodiesterase inhibitors show promise as pharmacotherapeutic agents 374... 

One of the primary mechanisms for regulation of phosphodiesterase enzyme activity is phosphorylation. 

There are a variety of structural classes of compounds that are active against each phosphodiesterase, and evidence suggests that selective inhibitors of PDEs can be identified. The structural diversity of PDE inhibitors provides a multitude of opportunities for development of compounds with drug-like properties. Furthermore, phosphodiesterase inhibition, which avoids direct interaction of a compound with a cell surface or nuclear receptor, may circumvent some of the target selectivity issues that can complicate receptor-based therapeutic approaches. As noted above, the specific subcellular distribution of phosphodiesterase enzymes is a key feature of their ability to modulate intracellular signaling pathways. This localization of the enzyme may minimize non-specific target... 

The nucleotide cyclic AMP (3, 5 -cyclic adenosine monophosphate, cAMP) is a cyclic phosphate ester of particular biochemical significance. It is formed from the triester ATP by the action of the enzyme adenylate cyclase, via nucleophilic attack of the ribose 3 -hydroxyl onto the nearest P=0 group, displacing diphosphate as leaving group. It is subsequently inactivated by hydrolysis to 5 -AMP through the action of a phosphodiesterase enzyme. 

Mechanism of Action A blood modifier and platelet aggregation inhibitor that inhibits the activity of adenosine deaminase and phosphodiesterase, enzymes causing accumulation of adenosine and cyclic adenosine monophosphate. Therapeutic Effect Inhibits platelet aggregation may cause coronary vasodilation. 

Plenty of biological activities have been attributed to derivatives of ring systems 1-50 in the patent and published literature. New substituted pyrazolo[4,3- pyrimidines have been synthesized and claimed to be useful for treatment of male erectile dysfunction due to the inhibitory action they exerted on phosphodiesterase enzymes <1998EPP995750, 2000USP6066722>. Diverse biological activities have been attributed to pyrazolo[3,4-, pyrimidines... 

Dipyridamole exerts its antiplatelet action by several mechanisms [7]. One of these is through the inhibition of phosphodiesterase enzyme in platelets, resulting in an increase in intraplatelet cyclic AMP and the consequent potentiation of the platelet inhibiting actions of prostacyclin. Another is the direct stimulation of the release of this eicosanoid by vascular endothelium, and the third is the inhibition of cellular uptake and metabolism of adenosine (thereby increasing its concentration at the platelet vascular interface). 

An additional mechanism controlling cAMP levels is metabolism by a specific phosphodiesterase enzyme, a cAMP-dependent phosphodiesterase. Such an enzyme exists in ASM and catalyses the degradation of cAMP to 5 -adenosine monophosphate. 

Other useful enzyme inhibitors include acetazolamide (Diamox) (carboific anhydrase inhibitor) for the treatment of glaucoma, congestive heart failure, epilepsy and motion sickness (a very useful drug ). Sildenafil (Viagra), famous for treatment of impotence, inhibits a phosphodiesterase enzyme (PDE5) that is involved in the breakdown of ATP. 

Polynucleoside Monophosphates. - The isodideoxyadenosine containing dinucleotide (53) has been prepared by phosphoramidite chemistry as a potential HIV inhibitor which mimics the DNA terminus obtained by the incorporation of isoddATP by the enzyme. The physical properties of the dinucleotide have been investigated and indicate that it has a similar structure to that of ApA but is much more stable to the action of various phosphodiesterase enzymes. 

In recent years, not a few scientific articles have been published about the eoun-terfeiting of heibal preparations and dietary supplements intended for the treatment of male sexual dysfunction (erectile dysfunction). The earliest reports appeared around the turn of the millennium, soon after the introduction of the first phosphodiesterase enzyme inhibitor drag called sildenafil (Viagra ) in 1998 (Fig. 3.51). Subsequently, an increasing number of articles detected the illegal use of sildenafil or its analogues in preparations of heibal origin . 

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