Ticagrelor and Adenosine

The Effect of Ticagrelor on the Adenosine System

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.

Inclusion Criteria:

• Male sex
• Age 18-40 years
• Healthy
• Written informed consent

Exclusion Criteria:

• Smoking
• Hypertension (Blood pressure >140 mmHg and/or >90 mmHg - SBP/DBP-)
• Diabetes Mellitus (fasting glucose > 7.0 mmol/L or random > 11.0 mmol/L)
• History of any cardiovascular disease
• History of chronic obstructive pulmonary disease (COPD) or asthma
• Bleeding tendency
• Concomitant use of medication
• Renal dysfunction (MDRD < 60 ml/min)
• Liver enzyme abnormalities (ALAT > twice upper limit of normality)
• Thrombocytopenia (<150*109/ml)
• Second/third degree AV-block on electrocardiography