Dipyridamole

Dipyridamole

File:Dipyridamole.svg
Systematic (IUPAC) name
2,2',2'',2'''-(4,8-di(piperidin-1-yl)pyrimido[5,4-d]pyrimidine-2,6-diyl)bis(azanetriyl)tetraethanol
Clinical data
Trade names	Persantine
AHFS/Drugs.com	monograph
MedlinePlus	a682830
Pregnancy category	B
Legal status	UK: POM (Prescription only) US: ℞-only
Routes of administration	oral, IV
Pharmacokinetic data
Protein binding	99%
Metabolism	Hepatic
Biological half-life	Alpha (40 mins), Beta (10 Hours)
Identifiers
CAS Number	58-32-2 Y
ATC code	B01AC07 (WHO)
PubChem	CID: 3108
IUPHAR/BPS	4807
DrugBank	DB00975 Y
ChemSpider	2997 Y
UNII	64ALC7F90C Y
KEGG	D00302 Y
ChEBI	CHEBI:4653 Y
ChEMBL	CHEMBL932 Y
Chemical data
Formula	C24H40N8O4
Molecular mass	504.626 g/mol
SMILES OCCN(CCO)C(N=C1N2CCCCC2)=NC3=C1N=C(N(CCO)CCO)N=C3N4CCCCC4
InChI InChI=1S/C24H40N8O4/c33-15-11-31(12-16-34)23-26-20-19(21(27-23)29-7-3-1-4-8-29)25-24(32(13-17-35)14-18-36)28-22(20)30-9-5-2-6-10-30/h33-36H,1-18H2 Y Key:IZEKFCXSFNUWAM-UHFFFAOYSA-N Y
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Dipyridamole (trademarked as Persantine) is a medication that inhibits blood clot formation when given chronically and causes blood vessel dilation when given at high doses over a short time.

Mechanism and effects

• Dipyridamole inhibits the phosphodiesterase enzymes that normally break down cAMP (increasing cellular cAMP levels and blocking the platelet aggregation response to ADP) and/or cGMP.

• It inhibits the cellular reuptake of adenosine into platelets, red blood cells, and endothelial cells leading to increased extracellular concentrations of adenosine.

Medical uses

• Dipyridamole is used to dilate blood vessels in people with peripheral arterial disease and coronary artery disease
• Dipyridamole has been shown to lower pulmonary hypertension without significant drop of systemic blood pressure
• It inhibits formation of pro-inflammatory cytokines (MCP-1, MMP-9) in vitro and results in reduction of hsCRP in patients.
• It inhibits proliferation of smooth muscle cells in vivo and modestly increases unassisted patency of synthetic arteriovenous hemodialysis grafts.
• It increases the release of t-PA from brain microvascular endothelial cells
• It results in an increase of 13-HODE and decrease of 12-HETE in the subendothelial matrix (SEM) and reduced thrombogenicity of the SEM.
• Pretreatment it reduced reperfusion injury in volunteers.
• It has been shown to increase myocardial perfusion and left ventricular function in patients with ischemic cardiomyopathy.
• It results in a reduction of the number of thrombin and PECAM-1 receptors on platelets in stroke patients.
• cAMP impairs platelet aggregation and also causes arteriolar smooth muscle relaxation. Chronic therapy did not show significant drop of systemic blood pressure.
• It inhibits the replication of mengovirus RNA.
• It can be used for myocardial stress testing as an alternative to exercise-induced stress methods such as treadmills.

Use in individuals with a history of stroke

A combination of dipyridamole and aspirin (Acetylsalicylic acid/dipyridamole) is FDA-approved for the secondary prevention of stroke and has a bleeding risk equal to that of aspirin use alone. Dipyridamole absorption is pH-dependent and concomitant treatment with gastric acid suppressors (such as a proton pump inhibitor) will inhibit the absorption of liquid & plain tablets. Modified release preparations are buffered and absorption is not affected.

However, it is not licensed as monotherapy for stroke prophylaxis, although a Cochrane Review suggested that dipyridamole may reduce the risk of further vascular events in patients presenting after cerebral ischemia.

A triple therapy of aspirin, clopidogrel, and dipyridamole has been investigated, but this combination led to an increase in adverse bleeding events.

• Vasodilation occurs in healthy arteries, whereas stenosed arteries remain narrowed. This creates a "steal" phenomenon where the coronary blood supply will increase to the dilated healthy vessels compared to the stenosed arteries which can then be detected by clinical symptoms of chest pain, electrocardiogram and echocardiography when it causes ischemia.
• Flow heterogeneity (a necessary precursor to ischemia) can be detected with gamma cameras and SPECT using nuclear imaging agents such as Thallium-201, Tc99m-Tetrofosmin and Tc99m-Sestamibi. However, relative differences in perfusion do not necessarily imply any absolute decrease in blood supply in the tissue supplied by a stenosed artery.

Other uses

Dipyridamole also has non-medicinal uses in a laboratory context, such as the inhibition of cardiovirus growth in cell culture.

Overdose

Dipyridamole overdose
Classification and external resources
Specialty
ICD-10	T46.3
ICD-9-CM	972.4
DiseasesDB	3840
Patient UK	Dipyridamole

Dipyridamole overdose can be treated with aminophylline which reverses its dilating effect on the blood vessels. Symptomatic treatment is recommended, possibly including a vasopressor drug. Gastric lavage should be considered. Administration of xanthine derivatives (e.g., aminophylline) may reverse the hemodynamic effects of dipyridamole overdose. Since dipyridamole is highly protein bound, dialysis is not likely to be of benefit.

See also

• Cilostazol