Ocular Applications of Dipyridamole: A Review of Indications and Routes of Administration

Abstract

Dipyridamole was introduced decades ago as a treatment for angina, subsequently found to inhibit platelet aggregation. It is most commonly used, and approved for use in thromboembolism prevention, following surgery. Some of its recognized effects such as adenosine uptake inhibition, elevation of cAMP and cGMP levels, vasodilation, and tissue perfusion are important in various ocular disorders. For this reason, dipyridamole represents an interesting candidate as a therapeutic target for the treatment of eye disorders affecting different ocular structures. The aim of this article is to review the evidence and current understanding of the mechanisms by which dipyridamole exerts its effects on different ocular tissues, discuss the role of dipyridamole in clinical practice, and highlight areas of use and routes of administration.

Adenosine modulators and calcium channel blockers as add-on treatment for schizophrenia

“…Allopurinol is a xanthine oxidase inhibitor which inhibits purine degradation and consequently, is thought to result in increased adenosine levels 7 . Dipyridamole increases extracellular adenosine levels by inhibiting adenosine reuptake to the erythrocytes, platelets, and endothelial cells 8 . Antipsychotics block dopamine D2-receptors 1 , and since adenosine agonists and antagonists produce opposite effects than dopamine agonists and antagonists, use of adenosine agonists, such as allopurinol and dipyridamole, could be beneficial in schizophrenia 7 , 11 .…”

“…Therefore, there is a theoretical basis for using adenosine agonists, such as allopurinol and dipyridamole, as add-on treatment for schizophrenia. Both of these drugs are believed to increase extracellular adenosine levels 7 , 8 . Allopurinol is used to treat gout, whereas dipyridamole is an antithrombotic and vasodilator 8 , 9 .…”

“…Both of these drugs are believed to increase extracellular adenosine levels 7 , 8 . Allopurinol is used to treat gout, whereas dipyridamole is an antithrombotic and vasodilator 8 , 9 . To the best of our knowledge, previous studies on allopurinol and dipyridamole as add-on treatment for schizophrenia have been small randomized controlled trials (RCTs) with somewhat heterogeneous results 6 , 10 – 13 .…”

Human neural progenitor cells decrease photoreceptor degeneration, normalize opsin distribution and support synapse structure in cultured porcine retina

“…Dipyridamole is a phosphodiesterase inhibitor that is normally used in the clinic as an anti-thrombotic drug (148); additionally, it is also a potent inhibitor of ENT1, as well as ENT2-4 with varying sensitivities (124). Furthermore, this drug has previously been investigated in different ocular disorders, using different routes of administration, such as intravitreal and oral, with no noted side effects (149). Interestingly, dipyridamole has been previously shown to reduce plasma uridine levels alone and in combination with PALA, an inhibitor of the aspartate transcarbamoylase activity of CAD, in cancer patients.…”

“…To enhance the therapeutic effect of brequinar, we considered whether simultaneous blocking of the salvage synthesis pathway of pyrimidine ribonucleotides would give a synergistic effect. We selected a human ENT1 inhibitor, dipyridamole, based on its current use in the clinic, and also because it was previously investigated to mitigate several ocular disorders (149).…”