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Safety issues of compounds acting on adenosinergic signalling
Jan Schmidt1,2, Polonca Ferk2
1Faculty of Chemistry and Chemical Engineering, University of Maribor, Maribor, Slovenia.
The Journal of Pharmacy and Pharmacology
|April 12, 2017
Summary
Adenosine receptor (AdR) ligands face safety challenges, limiting approvals. This review examines toxicological data and adverse effects of compounds targeting adenosinergic signaling, including novel pharmaceutical developments.
Area of Science:
- Pharmacology
- Toxicology
- Medicinal Chemistry
Background:
- Extensive research exists on adenosine and adenosinergic signaling roles.
- Limited marketing authorizations for adenosine receptor (AdR) ligands suggest underlying safety concerns.
Purpose of the Study:
- To examine toxicological and adverse effect data for compounds modulating adenosinergic signaling.
- To review pharmaceutical developments of experimental compounds in clinical trials.
Main Methods:
- Review of safety data for adenosine, adenosine derivatives, and non-nucleoside compounds.
- Analysis of mechanisms contributing to adverse effects and toxic outcomes.
- Examination of organ-specific toxic effects using in vitro and in vivo models.
Main Results:
- Compounds modulating adenosinergic signaling exhibit safety issues.
- Non-selective AdR ligands and compounds targeting related enzymes or other systems (e.g., GABA receptors) present risks.
- Some synthetic AdR ligands demonstrate genotoxicity.
Conclusions:
- This review consolidates safety data for various compounds affecting adenosinergic signaling.
- Understanding diverse mechanisms of toxicity is crucial for AdR ligand development.
- Organ-specific toxic effects require further investigation.
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