Avtor/Urednik		Schmidt, Jan; Ferk, Polonca
Naslov		Safety issues of compounds acting on adenosinergicsignalling
Tip		članek
Vol. in št.		Letnik 69, št. 7
Leto izdaje		2017
Obseg		str. 790-806
ISSN		2042-7158 - The Journal of pharmacy and pharmacology
Jezik		eng
Abstrakt		Objectives Much research has been performed on the feld of identifying the roles of adenosine and adenosinergic signalling, but a relatively low number ofmarketing authorizations have been granted for adenosine receptor (AdR) ligands. In part, this could be related to their safety issues; therefore, our aim wasto examine the toxicological and adverse effects data of different compounds act-ing on adenosinergic signalling, including different AdR ligands and compounds resembling the structure of adenosine. We also wanted to present recent pharma-ceutical developments of experimental compounds that showed promising results in clinical trial setting. Key endings Safety issues of compounds modulating adenosinergic signalling were investigated, and different mechanisms were presented. Structurally differ-ent classes of compounds act on AdRs, the most important being adenosine, ade-nosine derivatives and other non-nucleoside compounds. Many of them areeither not selective enough or are targeting other targets of adenosinergic sig-nalling such as metabolizing enzymes that regulate adenosine levels. Many othertargets are also involved that are not part of adenosinergic signalling system such as GABA receptors, different channels, enzymes and others. Some synthetic AdRligands even showed to be genotoxic. Summary Current review presents safety data of adenosine, adenosine deriva-tives and other non-nucleoside compounds that modulate adenosinergic sig-nalling. We have presented different mechanisms that participate to an adverseeffect or toxic outcome. A separate section also deals with possible organ-specictoxic effects on different in-vitro and in-vivo models.
Proste vsebinske oznake		adenosine adenosine derivatives adenosinereceptor ligands adenosinergic signalling mechanisms of toxicity