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Preclinical studies have shown that the P2Y12 receptor antagonist ticagrelor can increase the extracellular concentration of the endogenous nucleoside adenosine by inhibiting the cellular uptake of adenosine via the equilibrative nucleoside transporter (ENT). This mechanism can contribute to the beneficial effects and to the side effects (dyspnea) of ticagrelor in patients with an acute myocardial infarction. In the current research proposal, we aim to investigate whether ticagrelor increases adenosine receptor stimulation in humans in vivo by ENT inhibition.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ticagrelor 180 mg single dose | Active Comparator | Ticagrelor 180 mg single dose |
|
| Placebo | Placebo Comparator | Placebo single dose |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ticagrelor 180 mg single dose | Drug |
| ||
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Forearm blood flow response | Forearm blood flow response to the intrabrachial administration of incremental dosages of adenosine, after treatment with ticagrelor compared to placebo. The forearm blood flow will be measured by plethysmography. | 2 hours after intake of ticagrelor/placebo |
| Forearm blood flow response | Directly after 2 and 5 minutes of forearm ischemia.The forearm blood flow will be measured by plethysmography. | Directly after 2 and 5 minutes of forearm ischemia |
| Measure | Description | Time Frame |
|---|---|---|
| Forearm blood flow respons | Forearm blood flow response to the intrabrachial administration of incremental dosages of dipyridamole, after treatment with ticagrelor compared to placebo. The forearm blood flow will be measured by plethysmography | Directly after administration of dipyridamole |
| ex-vivo adenosine uptake in isolated erythrocytes |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| N. Riksen, MD, PhD | Radboud University Medical Center | Principal Investigator |
| G. Rongen, MD, PhD | Radboud University Medical Center | Principal Investigator |
| M. Gomes, MD, PhD | Dept Cardiology, Canisius Wilhelmina Hospital Nijmegen | Principal Investigator |
| S. El Messaoudi, MD | Radboud University Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Radboud University Nijmegen Medical Centre | Nijmegen | Gelderland | 6500 HB | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26509673 | Derived | van den Berg TN, El Messaoudi S, Rongen GA, van den Broek PH, Bilos A, Donders AR, Gomes ME, Riksen NP. Ticagrelor Does Not Inhibit Adenosine Transport at Relevant Concentrations: A Randomized Cross-Over Study in Healthy Subjects In Vivo. PLoS One. 2015 Oct 28;10(10):e0137560. doi: 10.1371/journal.pone.0137560. eCollection 2015. |
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| ID | Term |
|---|---|
| D000077486 | Ticagrelor |
| ID | Term |
|---|---|
| D000241 | Adenosine |
| D011684 | Purine Nucleosides |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
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|
To study whether ticagrelor inhibits the ex-vivo adenosine uptake in isolated erythrocytes |
| 2 hours after intake of studymedication |
| D000072471 |
| Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |