A Comprehensive Monograph on Dipyridamole (DB00975)

Executive Summary

Dipyridamole is a pyrimidopyrimidine-derived small molecule with a long-standing and evolving role in cardiovascular medicine. Classified primarily as an antiplatelet agent, it possesses a unique dual mechanism of action that distinguishes it from other drugs in its class, involving both the inhibition of phosphodiesterase (PDE) enzymes and the blockade of cellular adenosine reuptake.[1] This multifaceted pharmacology underpins its diverse clinical applications and ongoing investigational potential.

The core clinical utility of dipyridamole is well-defined by several key regulatory approvals. It is indicated as an adjunctive therapy to warfarin for the prophylaxis of thromboembolism following cardiac valve replacement surgery. In combination with low-dose aspirin as the extended-release product Aggrenox, it is a cornerstone for the secondary prevention of ischemic stroke and transient ischemic attacks (TIAs). Furthermore, its potent vasodilatory properties are harnessed in its intravenous formulation, which serves as a pharmacological stress agent for myocardial perfusion imaging in patients unable to undergo exercise-based testing.[3]

The therapeutic effects of dipyridamole are derived from its ability to increase intracellular levels of the second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), and to elevate extracellular concentrations of adenosine. These actions collectively inhibit platelet aggregation and induce significant vasodilation.[6] This vasodilatory property, while crucial for its diagnostic use, is also the source of its most common side effects, including headache and dizziness, and gives rise to the clinically significant "coronary steal" phenomenon in patients with advanced coronary artery disease.[3]