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Further Insights Into the Pharmacology of the Human Trace Amine‐Associated Receptors: Discovery of Novel Ligands for TAAR 1 by a Virtual Screening Approach
Author(s) -
Cichero Elena,
Espinoza Stefano,
Franchini Silvia,
Guariento Sara,
Brasili Livio,
Gainetdinov Raul R.,
Fossa Paola
Publication year - 2014
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12367
Subject(s) - virtual screening , pharmacology , drug discovery , receptor , chemistry , dopaminergic , g protein coupled receptor , biochemistry , neuroscience , biology , dopamine
Trace Amine‐Associated Receptor 1 ( TAAR 1) is a G protein‐coupled receptor that is expressed in brain and periphery and responds to a class of compounds called trace amines, such as β ‐phenylethylamine ( β ‐PEA ), tyramine, tryptamine, octopamine. The receptor is known to have a very rich pharmacology and could be also activated by different classes of compounds, including dopaminergic, adrenergic and serotonergic ligands. It is expected that targeting h TAAR 1 could provide a novel pharmacological approach for several human disorders, such as schizophrenia, depression, attention deficit hyperactivity disorder, Parkinson's disease and metabolic diseases. Only recently, a small number of selective h TAAR 1 agonists (among which RO5166017 and T 1 AM ) and antagonist ( EPPTB ), have been reported in literature. With the aim to identify new molecular entities able to act as ligands for this target, we used an homology model for the h TAAR 1 and performed a virtual screening procedure on an in‐house database of compounds. A number of interesting molecules were selected and by testing them in an in vitro assay we found several agonists and one antagonist, with activities in the low micromolar range. These compounds could represent the starting point for the development of more potent and selective TAAR 1 ligands.