Trace Amine-Associated Receptor 1 Partial Agonism Reveals Novel Paradigm for Neuropsychiatric Therapeutics

@article{Revel2012TraceAR,
  title={Trace Amine-Associated Receptor 1 Partial Agonism Reveals Novel Paradigm for Neuropsychiatric Therapeutics},
  author={Florent G. Revel and J. -L. Moreau and Raul R. Gainetdinov and Antonio Ferragud and Clara Vel{\'a}zquez-S{\'a}nchez and Tatyana D. Sotnikova and Stephen R. Morairty and Anja Harmeier and Katrin Groebke Zbinden and Roger David Norcross and Amyaouch Bradaia and Thomas S. Kilduff and Barbara Agatha Maria Biemans and Bruno Pouzet and Marc G. Caron and Juan J Canales and Tanya L Wallace and Joseph G. Wettstein and Marius C. Hoener},
  journal={Biological Psychiatry},
  year={2012},
  volume={72},
  pages={934-942}
}
BACKGROUND Trace amines, compounds structurally related to classical biogenic amines, represent endogenous ligands of the trace amine-associated receptor 1 (TAAR1). Because trace amines also influence the activity of other targets, selective ligands are needed for the elucidation of TAAR1 function. Here we report on the identification and characterization of the first selective and potent TAAR1 partial agonist. METHODS The TAAR1 partial agonist RO5203648 was evaluated for its binding affinity… 
Trace amine-associated receptor 1: a multimodal therapeutic target for neuropsychiatric diseases
TLDR
A combination of preclinical and translationally driven studies has solidified TAAR1 as a key node in the regulation of dopaminergic signaling and holds great promise as a therapeutic target for mental illness, addiction, and sleep disorders.
Behavioral Effects of a Potential Novel TAAR1 Antagonist
TLDR
The results showed that compound 22 is able to enhance amphetamine- and cocaine-mediated locomotor activity, even in TAAR1-KO mice, suggesting that the in vivo effects of this compound are not mediated byTAAR1, and the biological target of compound 22 mediating its psychoactive effects still remains unknown.
In Vitro Characterization of Psychoactive Substances at Rat, Mouse, and Human Trace Amine-Associated Receptor 1
TLDR
Pharmacological in vitro profiles of 101 psychoactive substances at human, rat, and mouse TAAR1 are presented and considerable species differences in activity are found among the highly active ligands, with a rank order of rat > mouse > human, which provides information about the pharmacological profile of psycho active substances.
Trace Amines and the Trace Amine-Associated Receptor 1: Pharmacology, Neurochemistry, and Clinical Implications
TLDR
TAAR1 is uniquely positioned to exert direct control over DA and 5-HT neuronal firing and release, which has profound implications for understanding the pathophysiology of, and therefore designing more efficacious therapeutic interventions for, a range of neuropsychiatric disorders that involve aminergic dysregulation.
Amphetamines Activate G-Protein Coupled Trace Amine-Associated Receptor 1 (TAAR1)
Abstract Trace amine-associated receptor 1 (TAAR1) shares significant nucleotide and amino acid sequence identity with dopamine, adrenergic, and serotonergic receptors. Heterologously expressed in
Further Insights Into the Pharmacology of the Human Trace Amine‐Associated Receptors: Discovery of Novel Ligands for TAAR1 by a Virtual Screening Approach
TLDR
An homology model for the hTAAR1 was used and several agonists and one antagonist, with activities in the low micromolar range were found, which could represent the starting point for the development of more potent and selective TAAR1 ligands.
Deletion of Trace Amine-Associated Receptor 1 Attenuates Behavioral Responses to Caffeine
TLDR
It is reported that locomotor and EEG spectral responses to the psychostimulants modafinil and caffeine are attenuated in TAAR1 KO mice, and this data suggest that TAar1 is a previously unrecognized component of an endogenous wake-modulating system.
Neuronal Functions and Emerging Pharmacology of TAAR1
TLDR
Brain and peripheral functions mediated by TAAR1 and other TAARs are reviewed, suggesting intriguing novelTAAR1 roles in system physiology.
Trace Amine-Associated Receptor 1 Modulation of Dopamine System
TLDR
TAAR1 can modulate monoamine neurotransmission and, in particular, the dopamine system, and has been proposed as a novel therapeutic target for neuropsychiatric disorders such as schizophrenia, bipolar disorder, and addiction.
In-vivo pharmacology of Trace-Amine Associated Receptor 1.
TLDR
It is indicated that TAar1 is a negative regulator of dopamine transmission making TAAR1 a novel target for neuropsychiatric disorders that arises from dopamine dysfunction such as schizophrenia.
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It is expected that further characterization of the functional roles and biochemical properties of TAARs and identification of endogenous and exogenous ligands will eventually promote these receptors as an attractive class of targets to correct monoaminergic processes that could be dysfunctional in a host of disorders of brain and periphery.
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