Receptorome screening: a powerful, facile approach to better understand and engineer drugs.
Receptorome screening is the process of characterizing one or more compounds for pharmacological activity (e.g., inhibition of radioligand binding, positive or negative efficacy) at a large panel of 'targets' (e.g., biologically relevant recombinant G protein-coupled receptors, ion channels and small-molecule transporters). Recently, receptorome profiles have led to mechanistic insights into the actions -both intentional and adverse- of several drugs. In the present review, I discuss in detail how receptorome screening increased our understanding of three drugs (salvinorin A, amisulpride and fenfluramine) and a class of medications (atypical antipsychotics). The cases presented suggest that receptorome screening of current medications, as well as investigational drugs and future compounds destined for use in humans, might enable us to predict salutary effects, as well as side effects, at the preclinical stage, which would have important economic and public health implications.
Setola
Vincent
V
Department of Pharmacology of the University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. vsetola@gmail.com
D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000494:pharmacology; D045785:Diterpenes, Clerodane / Q000009:adverse effects / Q000494:pharmacology; D016503:Drug Delivery Systems; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D015507:Drugs, Investigational / Q000009:adverse effects / Q000494:pharmacology; D005277:Fenfluramine / Q000009:adverse effects / Q000494:pharmacology; D006801:Humans; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism
D014150:Antipsychotic Agents; D045785:Diterpenes, Clerodane; D015507:Drugs, Investigational; D011956:Receptors, Cell Surface; D005277:Fenfluramine; C090499:salvinorin A