@Article{Śniecikowska2017,
journal="Advances in Psychiatry and Neurology/Postępy Psychiatrii i Neurologii",
issn="1230-2813",
volume="26",
number="3",
year="2017",
title="Functional selectivity – chance for better and safer drugs?",
abstract=" Purpose : The  article reviews the  current state of  knowledge about functional selectivity (biased agonism) at G protein-coupled receptors (GPCRs), with a  particular focus on serotonin 5-HT 1A  receptors.   Views:   Recently, functional selectivity has been one of  the  fastest growing topics in GPCRs pharmacology. Research on this phenomenon allowed identification of  signal transduction pathways which can be preferentially targeted to achieve improved therapeutic effects or, conversely, which are associated with adverse effects. Oliceridine, a  phase III clinical candidate for treatment of  pain, is an  example of  a  functionally selective ligand of  µ-opioid receptors that preferentially activates signal transduction via G proteins rather than β-arrestin. Biased agonism, or the  ability to preferentially activate specific signalling pathways, has been identified for many therapeutically important GPCRs, such as µ-opioid receptors, α 1-  and β 2 -adrenoceptors, dopamine D2 L  and D 1  receptors, angiotensin 1A receptor, as well as 5-HT 2  and 5-HT 1A  serotonin receptors. The  recently discovered compounds F15599 and F13714 have been identified as functionally and regionally selective ligands of  5-HT 1A  receptors. These compounds constitute a  new generation of  pharmacological tools with high therapeutic potential, which is currently being investigated for the  treatment of  disorders including Parkinson’s disease, depression and Rett syndrome.   Conclusions:   Functional selectivity (biased agonism) enables separation of  the  therapeutic effect from the  adverse effects, so far considered to be intrinsically linked to the  mechanism of  action, by preferentially targeting signal transduction pathways associated with beneficial effects. It may therefore offer new opportunities for improved development of  more effective and safer drugs.",
author="Śniecikowska, Joanna
and Głuch-Lutwin, Monika
and Bucki, Adam
and Mierzejewski, Paweł
and Kołaczkowski, Marcin",
pages="165--178",
doi="10.5114/ppn.2017.70548",
url="http://dx.doi.org/10.5114/ppn.2017.70548"
}