Cilostazol is a PDE3 inhibitor which is used for the treatment of intermittent claudication. The drug positively affects the platelet aggregation and may be used off-label as a measure to prevent coronary thrombosis/restenosis and stroke recurrence.

Anagrelide is an orally active quinazinolone derivative that was originally developed as an antiplatelet drug. The drug inhibits cyclic nucleotide phosphodiesterase III (PDEIII) and phopholipase A2, which is thought to cause the side effects of vasodilation, positive inotropism, reduced platelet aggregation. However, significant inhibition of platelet aggregation is observed only at doses of anagrelide higher than those required to reduce platelet count. It is indicated for the treatment of patients with thrombocythemia, secondary to myeloproliferative disorders. Commonly reported side effects of anagrelide include: abdominal pain, dizziness, headache, nausea, and palpitations. Other side effects include: back pain, fever, tachycardia, vomiting, and anorexia. There is a single case report, which suggests that sucralfate may interfere with anagrelide absorption. Anagrelide is an inhibitor of cyclic AMP PDE III. The effects of medicinal products with similar properties such as inotropes milrinone, enoximone, amrinone, olprinone and cilostazol may be exacerbated by anagrelide.

Since its discovery as component of the tea leaf by Albert Kossel in 1888, the history of theophylline (CAS 58-55-9) has been a long and successful one. At the turn of the century, theophylline became less expensive due to chemical synthesis and was primarily used as diuretic in subsequent years. It was Samuel Hirsch who discovered the bronchospasmolytic effect of theophylline in 1992, however, despite this pioneering discovery theophylline continued to be used primarily as diuretic and cardiac remedy. The molecular mechanism of bronchodilatation is inhibition of phosphodiesterase(PDE)3 and PDE4, but the anti-inflammatory effect may be due to histone deacetylase (HDAC) activation, resulting in switching off of activated inflammatory genes. Theophylline is indicated for the treatment of acute exacerbations of the symptoms and reversible airflow obstruction associated with asthma and other chronic lung diseases, e.g., emphysema and chronic bronchitis.

Pelrinone, a cardiotonic drug, is a phosphodiesterase III inhibitor that was studied in clinical trials phase II for the treatment of patients with heart failure.

NT-702 (parogrelil hydrochloride) is a novel phosphodiesterase 3 (PDE) inhibitor, and being developed for the treatment of intermittent claudication (IC) in patients with peripheral arterial disease. In Japan, Phase 2 studies are being conducted for intermittent claudication caused by arteriosclerosis obliterans, intermittent claudication caused by spinal canal stenosis, and asthma. In the USA, a Phase 2 study for intermittent claudication caused by arteriosclerosis obliterans has been successfully completed. Also was shown, that NT-702 has an anti-inflammatory effect as well as a bronchodilating effect and might be useful as a novel potent therapeutic agent with both a bronchodilating and an anti-inflammatory effect.

Sulrnazole (the former AR-L 115 BS) is a benzimidazole derivative with positive inotropic, positive chronotropic and vasodilator effects. Sulrnazole also has been shown to improve cardiac index and reduce pulmonary capillary wedge pressure without significant change in heart rate or arterial pressure. Intravenous administration caused a 217 per cent increase in cardiac output with a 25 per cent decrease in pulmonary wedge pressure. Short-term oral administration resulted in a 317 per cent increase in cardiac index and a 317 per cent increase in ejection fraction. Side effects have included visual blurring and transient colour blindness. Sulmazol has been demonstrated to improve regional wall motion in patients with ischemic heart disease and to abolish pacing-induced ischemia. Sulrnazole is an A1 adenosine receptor antagonist. It is also a phosphodiesterase inhibitor.

Trequinsin is a potent PDE3 inhibitor that inhibits PDE4 and PDE2 at higher concentrations. Trequinsin can block platelet aggregation and also inhibit tissue factor expression in human endothelial cells. Trequinsin can enhance cellular cAMP content, forskolin-induced cAMP synthesis, and renin release in cells.

Tolafentrine is phosphodiesterase 3/4 (PDE3/4) inhibitor. Treatment of endothelial cells with tolafentrine significantly decreased asymmetrical dimethylarginine-induced apoptosis via a cAMP/PKA-dependent pathway by induction of dimethylarginine dimethylaminohydrolase 2 (DDAH2). Chronic nebulization of PDE3/4 inhibitor significantly attenuated monocrotaline-induced hemodynamic, gas exchange abnormalities, vascular remodeling, and right heart hypertrophy. When chronically nebulized from day 28 to 42 (12 daily aerosol maneuvers), after full establishment of severe pulmonary hypertension, tolafentrine reversed about 60% of all hemodynamic abnormalities in rats, right heart hypertrophy and monocrotaline-induced structural lung vascular changes, including the proportion of pulmonary artery muscularization. Tolafentrine was developed as therapeutic agent for the treatment of asthma. However, this development was discontinued.

Motapizone is a pyridazinone derivative patented by pharmaceutical company Nattermann, A., und Cie. G.m.b.H. as an antithrombotic and hypotensive agent. Motapizone ats as a potent inhibitor of the isoenzyme phophodiesterase type III. In preclinical studies potent antithrombotic and hypotensive properties of motapizone has been shown in rats, cats, and dogs. In normal human volunteers, single oral doses of motapizone up to 10 mg produced significant inhibition of platelet aggregation measured by the ex vivo method. These effects were dependent upon the dose of motapizone and associated with an increase in heart rate and a reduction in diastolic blood pressure.

Revizinone (R-80122) is a selective phosphodiesterase (PDE) III inhibitor, developed for use in treatment of heart failure and ischaemic heart disorders. Revizinone showed positive inotropic and possibly moderate vasodilating properties in dogs, and it was concluded that revizinone has a clinically favorable cardiovascular profile for acute applications in heart failure. In patients with impaired left ventricular function, revizinone was also found to be a potent positive inotropic agent. The drug was safe, its use not associated with marked vasodilation, and no positive chronotropic effects were reported.