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A review of the effects of ticagrelor on adenosine concentration and its clinical significance

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Abstract

Background

Ticagrelor is an oral antiplatelet drug that can reversibly bind to the platelet P2Y12 receptor. Ticagrelor is metabolized mainly by CYP3A4 and produces a rapid blood concentration-dependent platelet inhibitory effect. Unlike other P2Y12 receptor antagonists, many clinical features of ticagrelor are not related to P2Y12 receptor antagonism.

Purpose

This review aims to gather existing literature on the clinical effects of ticagrelor after inhibiting adenosine uptake.

Methodology

The current study reviewed literature related to the effects of ticagrelor on adenosine metabolism. The review also examined the drug's biological effects and clinical characteristics to see how it could be used in a clinical setting.

Results

Many studies have shown that ticagrelor can inhibit equilibrative nucleoside transporter 1 (ENT1). This inhibition leads to intracellular adenosine uptake, increased adenosine half-life and plasma concentration levels and an enhanced adenosine-mediated biological effect.

Conclusions

Based on the studies reviewed, it was found that ticagrelor essentially inhibits adenosine absorption of adenosine into cells through ENT1, which increases the concentration in the blood and subsequently increases the protection of the heart muscle by adenosine. It also prevents platelet aggregation, and extends the biological effects of coronary arteries. Moreover, it leads to a lower mortality rate in acute coronary syndrome (ACS) patients.

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Fig. 1

Copyright© 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved

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Abbreviations

ACS:

Acute coronary syndrome

ADP:

Adenosine diphosphate

AMI:

Acute myocardial infarction

AMP:

Adenosine monophosphate

APC:

Adenosine plasma concentration

CAD:

Coronary artery disease

cAMP:

Cyclic adenosine monophosphate

ENT1:

Equilibrative nucleoside transporter 1

FAAK:

Fluorescent adenosine assay kits

HPLC:

High-performance liquid chromatography

LV:

Left ventricular

MI:

Myocardial infarction

NSTEMI:

Non-ST-segment elevation myocardial infarction

PCI:

Percutaneous coronary intervention

TIMI:

Thrombolysis in myocardial infarction

tPA:

Tissue plasminogen activator

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Authors and Affiliations

  1. School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800, Gelugor, Penang, Malaysia

    Mohammed Ahmed Akkaif, Nur Aizati Athirah Daud & Abubakar Sha’aban

  2. Advanced Medical and Dental Institute, Universiti Sains Malaysia, 13200, Gelugor, Penang, Malaysia

    Mei Li Ng

  3. Department of Cardiology, Penang General Hospital, 10990, George Town, Pulau Pinang, Malaysia

    Muhamad Ali SK Abdul Kader

  4. Faculty of Pharmacy, University of Malaya, 50603, Kuala Lumpur, Malaysia

    Baharudin Ibrahim

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Akkaif, M.A., Ng, M.L., SK Abdul Kader, M.A. et al. A review of the effects of ticagrelor on adenosine concentration and its clinical significance. Pharmacol. Rep 73, 1551–1564 (2021). https://doi.org/10.1007/s43440-021-00309-0

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