Dipyridamole, a non-nitrate coronary vasodilator that also inhibits platelet aggregation, is combined with other anticoagulant drugs, such as warfarin, to prevent thrombosis in patients with valvular or vascular disorders. Dipyridamole is also used in myocardial perfusion imaging, as an antiplatelet agent, and in combination with aspirin for stroke prophylaxis. Dipyridamole likely inhibits both adenosine deaminase and phosphodiesterase, preventing the degradation of cAMP, an inhibitor of platelet function. This elevation in cAMP blocks the release of arachidonic acid from membrane phospholipids and reduces thromboxane A2 activity. Dipyridamole also directly stimulates the release of prostacyclin, which induces adenylate cyclase activity, thereby raising the intraplatelet concentration of cAMP and further inhibiting platelet aggregation. Used for as an adjunct to coumarin anticoagulants in the prevention of postoperative thromboembolic complications of cardiac valve replacement and also used in prevention of angina.

Zaprinast is (M&B 22,948; 2-o-propoxy-phenyl-8-azapurin-6-one) is a selective inhibitor of cyclic GMP (cGMP)-dependent phosphodiesterases, with vasodilation activity in a variety of species and tissues. The potency of zaprinast as a vasorelaxant varies with the species, the tissue, and the presence and absence of endothelium. Zaprinast apparently loses all or most of its vasorelaxant capacity when arteries have been denuded of the endothelial cell layer. Alternatively, the vasorelaxant effects of zaprinast can be attenuated using methylene blue, an inhibitor of soluble guanylate cyclase and hemoglobin inhibitor of nitric oxide synthesis. Therefore, zaprinast-induced relaxations appear to be endothelium-dependent. In human platelets zaprinast, at a dose of 10 mkM, caused a modest (20%) inhibition of aggregation as well as a small increase in cGMP content. In anesthetized rats, zaprinast dose-dependently lowered mean arterial blood pressure (MAP), an effect that correlated well with increased levels of plasma cGMP. Zaprinast decreased mean arterial pressure, the reduction being inversely related to zaprinast concentration. Zaprinast had no effect on heart rate, but increased cardiac output, urinary output, urinary sodium excretion, as well as renal blood flow. Oral administration of zaprinast to spontaneously hypertensive rats at a dose of 200 mg/kg/day normalized blood pressure. In normotensive rats, however, no changes in blood pressure were observed with the same treatment. In an initial placebo-controlled, double-blind crossover trial, 10 mg of zaprinast was effective in reducing exercise-, but not histamine-induced bronchoconstriction in adult asthmatics. However, in a similar study with asthmatic children, zaprinast was ineffective in preventing exercise-induced bronchoconstriction. Since then the clinical development of zaprinast has been discontinued.

FILAMINAST is a phosphodiesterase 4 inhibitor with bronchorelaxant activity and selectivity of potential use in the treatment of asthma. However, its clinical development was discontinued due to lack of efficacy.

Zardaverine (6-(4-difluoromethoxy-3-methoxyphenyl)-3[2H]pyridazinone) is a dual-selective inhibitor of phosphodiesterase III/IV was developed as a potential therapeutic agent for asthma. Zardaverine has been shown to inhibit inflammatory cell function, human peripheral blood mononuclear cells (PBMC) and T-cell proliferation and exert a positive inotropic action on the heart muscle. In animals, zardaverine exhibits both bronchodilatory and anti-inflammatory activities. In order to study the efficacy and safety in man, Zardaverine has been tested in clinical trials for the treatment COPD and asthma. Zardaverine has a modest and short-lasting bronchodilatory effect in patients with asthma. However, due to its fast elimination, the development of zardaverine was terminated in 1991.

Dipyridamole, a non-nitrate coronary vasodilator that also inhibits platelet aggregation, is combined with other anticoagulant drugs, such as warfarin, to prevent thrombosis in patients with valvular or vascular disorders. Dipyridamole is also used in myocardial perfusion imaging, as an antiplatelet agent, and in combination with aspirin for stroke prophylaxis. Dipyridamole likely inhibits both adenosine deaminase and phosphodiesterase, preventing the degradation of cAMP, an inhibitor of platelet function. This elevation in cAMP blocks the release of arachidonic acid from membrane phospholipids and reduces thromboxane A2 activity. Dipyridamole also directly stimulates the release of prostacyclin, which induces adenylate cyclase activity, thereby raising the intraplatelet concentration of cAMP and further inhibiting platelet aggregation. Used for as an adjunct to coumarin anticoagulants in the prevention of postoperative thromboembolic complications of cardiac valve replacement and also used in prevention of angina.