title: Classical and pleiotropic actions of dipyridamole: Not enough light to illuminate the dark tunnel?
abstract: Dipyridamole is a platelet inhibitor indicated for the secondary prevention of transient ischemic attack. It inhibits the enzyme phosphodiesterase, elevates cAMP and cGMP levels and prevents platelet aggregation. Dipyridamole inhibits the cellular uptake of adenosine into red blood cells, platelets and endothelial cells that results in increased extracellular availability of adenosine, leading to modulation of cardiovascular function. The antiplatelet action of dipyridamole might offer therapeutic benefits in secondary stroke prevention in combination with aspirin. Inflammation and oxidative stress play an important role in atherosclerosis and thrombosis development, leading to stroke progression. Studies demonstrated anti-inflammatory, anti-oxidant and anti-proliferative actions of dipyridamole. These pleiotropic potentials of dipyridamole might contribute to improved therapeutic outcomes when used with aspirin in preventing secondary stroke. Dipyridamole was documented as a coronary vasodilator 5 decades ago. The therapeutic failure of dipyridamole as a coronary vasodilator is linked with induction of 'coronary steal' phenomenon in which by dilating resistance vessels in non-ischemic zone, dipyridamole diverts the already reduced blood flow away from the area of ischemic myocardium. Dipyridamole at high-dose could cause a marked 'coronary steal' effect. Dipyridamole, however, at low-dose could have a minimal hemodynamic effect. Low-dose dipyridamole treatment has a therapeutic potential in partially preventing diabetes mellitus-induced experimental vascular endothelial and renal abnormalities by enhancing endothelial nitric oxide signals and inducing renovascular reduction of oxidative stress. In spite of plenteous research on dipyridamole's use in clinics, its precise clinical application is still obscure. This review sheds lights on pleiotropic pharmacological actions and therapeutic potentials of dipyridamole.
authors.affiliation: Pharmacology Unit, Faculty of Pharmacy, Asian Institute of Medicine, Science and Technology (AIMST) University, Semeling, 08100 Bedong, Kedah Darul Aman, Malaysia. Electronic address: pbala2006@gmail.com.
authors.forename: Pitchai
authors.initials: P
authors.lastname: Balakumar
authors.affiliation: Pharmacology Unit, Faculty of Pharmacy, Asian Institute of Medicine, Science and Technology (AIMST) University, Semeling, 08100 Bedong, Kedah Darul Aman, Malaysia.
authors.forename: Ying Hui
authors.initials: YH
authors.lastname: Nyo
authors.affiliation: Pharmacology Unit, Faculty of Pharmacy, Asian Institute of Medicine, Science and Technology (AIMST) University, Semeling, 08100 Bedong, Kedah Darul Aman, Malaysia.
authors.forename: Raja
authors.initials: R
authors.lastname: Renushia
authors.affiliation: Pharmacology Unit, Faculty of Pharmacy, Asian Institute of Medicine, Science and Technology (AIMST) University, Semeling, 08100 Bedong, Kedah Darul Aman, Malaysia.
authors.forename: Devarajan
authors.initials: D
authors.lastname: Raaginey
authors.affiliation: Pharmacology Unit, Faculty of Pharmacy, Asian Institute of Medicine, Science and Technology (AIMST) University, Semeling, 08100 Bedong, Kedah Darul Aman, Malaysia.
authors.forename: Ann Nah
authors.initials: AN
authors.lastname: Oh
authors.affiliation: Pharmacology Unit, Faculty of Pharmacy, Asian Institute of Medicine, Science and Technology (AIMST) University, Semeling, 08100 Bedong, Kedah Darul Aman, Malaysia.
authors.forename: Rajavel
authors.initials: R
authors.lastname: Varatharajan
authors.affiliation: Pharmaceutical Technology Unit, Faculty of Pharmacy, AIMST University, Semeling, 08100 Bedong, Kedah Darul Aman, Malaysia.
authors.forename: Sokkalingam A
authors.initials: SA
authors.lastname: Dhanaraj
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D003928:Diabetic Nephropathies / Q000188:drug therapy; D004176:Dipyridamole / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D010726:Phosphodiesterase Inhibitors; D010975:Platelet Aggregation Inhibitors; D014665:Vasodilator Agents; D004176:Dipyridamole
keywords: Antiplatelet agent; Dipyridamole; Pleiotropic actions; Therapeutic potentials