TY - JOUR

T1 - Trace amine-associated receptor 1

T2 - a multimodal therapeutic target for neuropsychiatric diseases

AU - Schwartz, Michael D.

AU - Canales, Juan J.

AU - Zucchi, Riccardo

AU - Espinoza, Stefano

AU - Sukhanov, Ilya

AU - Gainetdinov, Raul R.

PY - 2018/6/3

Y1 - 2018/6/3

N2 - Introduction: The trace amines, endogenous amines closely related to the biogenic amine neurotransmitters, have been known to exert physiological and neurological effects for decades. The recent identification of a trace amine-sensitive G protein-coupled receptor, trace amine-associated receptor 1 (TAAR1), and subsequent development of TAAR1-selective small-molecule ligands, has renewed research into the therapeutic possibilities of trace amine signaling. Areas covered: Recent efforts in elucidating the neuropharmacology of TAAR1, particularly in neuropsychiatric and neurodegenerative disease, addiction, and regulation of arousal state, will be discussed. Focused application of TAAR1 mutants, synthetic TAAR1 ligands, and endogenous biomolecules such as 3-iodothyronamine (T1AM) has yielded a basic functional portrait for TAAR1, despite a complex biochemistry and pharmacology. The close functional relationship between TAAR1 and dopaminergic signaling is likely to underlie many of its CNS effects. However, TAAR1’s influences on serotonin and glutamate neurotransmission will also be highlighted. Expert opinion: TAAR1 holds great promise as a therapeutic target for mental illness, addiction, and sleep disorders. A combination of preclinical and translationally driven studies has solidified TAAR1 as a key node in the regulation of dopaminergic signaling. Continued focus on the mechanisms underlying TAAR1’s regulation of serotonin and glutamate signaling, as well as dopamine, will yield further disease-relevant insights.

AB - Introduction: The trace amines, endogenous amines closely related to the biogenic amine neurotransmitters, have been known to exert physiological and neurological effects for decades. The recent identification of a trace amine-sensitive G protein-coupled receptor, trace amine-associated receptor 1 (TAAR1), and subsequent development of TAAR1-selective small-molecule ligands, has renewed research into the therapeutic possibilities of trace amine signaling. Areas covered: Recent efforts in elucidating the neuropharmacology of TAAR1, particularly in neuropsychiatric and neurodegenerative disease, addiction, and regulation of arousal state, will be discussed. Focused application of TAAR1 mutants, synthetic TAAR1 ligands, and endogenous biomolecules such as 3-iodothyronamine (T1AM) has yielded a basic functional portrait for TAAR1, despite a complex biochemistry and pharmacology. The close functional relationship between TAAR1 and dopaminergic signaling is likely to underlie many of its CNS effects. However, TAAR1’s influences on serotonin and glutamate neurotransmission will also be highlighted. Expert opinion: TAAR1 holds great promise as a therapeutic target for mental illness, addiction, and sleep disorders. A combination of preclinical and translationally driven studies has solidified TAAR1 as a key node in the regulation of dopaminergic signaling. Continued focus on the mechanisms underlying TAAR1’s regulation of serotonin and glutamate signaling, as well as dopamine, will yield further disease-relevant insights.

KW - addiction

KW - depression

KW - Dopamine

KW - neuropharmacology

KW - psychostimulants

KW - schizophrenia

KW - serotonin

KW - sleep

UR - http://www.scopus.com/inward/record.url?scp=85048587008&partnerID=8YFLogxK

UR - http://www.mendeley.com/research/trace-amineassociated-receptor-1-multimodal-therapeutic-target-neuropsychiatric-diseases-1

U2 - 10.1080/14728222.2018.1480723

DO - 10.1080/14728222.2018.1480723

M3 - Review article

AN - SCOPUS:85048587008

VL - 22

SP - 513

EP - 526

JO - Expert Opinion on Therapeutic Targets

JF - Expert Opinion on Therapeutic Targets

SN - 1472-8222

IS - 6

ER -