A Non–D2-Receptor-Binding Drug for the Treatment of Schizophrenia

Koblan, Kenneth S.; Kent, Justine; Hopkins, Seth C.; Krystal, John H.; Cheng, Hailong; Goldman, Robert; Loebel, Antony

doi:10.1056/nejmoa1911772

Cited by 206 publications

(180 citation statements)

References 28 publications

Supporting

Mentioning

173

Contrasting

Order By: Relevance

“…The distribution of TAAR1 is predominantly intracellular thus being uniquely positioned to regulate aminergic activity (possibly including DAT function) (Asif-Malik et al, 2017). The recent positive clinical results obtained with the TAAR1 agonist SEP-363856 tested as antipsychotic provide a confirmation of the relevance of the observed alterations in presynaptic DA release in SCZ (Pei et al, 2016;Koblan et al, 2020).…”

Section: D2/d3 Receptorsmentioning

confidence: 88%

Dopamine Receptor Subtypes, Physiology and Pharmacology: New Ligands and Concepts in Schizophrenia

Martel¹,

McArthur²

2020

Front. Pharmacol.

150

125

View full text Add to dashboard Cite

Dopamine receptors are widely distributed within the brain where they play critical modulator roles on motor functions, motivation and drive, as well as cognition. The identification of five genes coding for different dopamine receptor subtypes, pharmacologically grouped as D1- (D1 and D5) or D2-like (D2S, D2L, D3, and D4) has allowed the demonstration of differential receptor function in specific neurocircuits. Recent observation on dopamine receptor signaling point at dopamine—glutamate-NMDA neurobiology as the most relevant in schizophrenia and for the development of new therapies. Progress in the chemistry of D1- and D2-like receptor ligands (agonists, antagonists, and partial agonists) has provided more selective compounds possibly able to target the dopamine receptors homo and heterodimers and address different schizophrenia symptoms. Moreover, an extensive evaluation of the functional effect of these agents on dopamine receptor coupling and intracellular signaling highlights important differences that could also result in highly differentiated clinical pharmacology. The review summarizes the recent advances in the field, addressing the relevance of emerging new targets in schizophrenia in particular in relation to the dopamine – glutamate NMDA systems interactions.

show abstract

Section: D2/d3 Receptorsmentioning

confidence: 88%

Dopamine Receptor Subtypes, Physiology and Pharmacology: New Ligands and Concepts in Schizophrenia

Martel¹,

McArthur²

2020

Front. Pharmacol.

150

125

View full text Add to dashboard Cite

show abstract

“…Interestingly, anti-psychotic drugs, pimavanserin and SEP-363856 have just been introduced that preferentially target serotonin and not dopamine receptors (93,94), suggesting increased focus also on serotonergic pathways.…”

Section: Molecular Architecture Of the Network Robustly Predicted Comentioning

confidence: 99%

Intrinsic Connectivity Patterns of Task-Defined Brain Networks Allow Individual Prediction of Cognitive Symptom Dimension of Schizophrenia and Are Linked to Molecular Architecture

Chen

Müller

Dukart

et al. 2021

Biological Psychiatry

View full text Add to dashboard Cite

show abstract

“…Many compounds, both selective and multi-target, have been generated to this end (30), and encouraging observations acquired in experimental and clinical studies (31). Most recently, the combined TAAR1/5-HT1AR agonist, SEP-363856, showed antipsychotic activity in schizophrenic patients (31,32). Should these observations be corroborated in larger trials SEP-363856 would become the first non-D2R antagonist available for the treatment of schizophrenia (31,32).…”

Section: Introductionmentioning

confidence: 99%

“…The above observations underpin interest in TAAR1 as a potential target for novel classes of medication treating depression (antagonists) or psychotic disorders (agonists). Many compounds, both selective and multi-target, have been generated to this end (30), and encouraging observations acquired in experimental and clinical studies (31). Most recently, the combined TAAR1/5-HT1AR agonist, SEP-363856, showed antipsychotic activity in schizophrenic patients (31,32).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

TAAR1-Dependent and -Independent Actions of Tyramine in Interaction With Glutamate Underlie Central Effects of Monoamine Oxidase Inhibition

Mantas

Vallianatou

Yang

et al. 2021

Biological Psychiatry

View full text Add to dashboard Cite

A Non–D2-Receptor-Binding Drug for the Treatment of Schizophrenia

Cited by 206 publications

References 28 publications

Dopamine Receptor Subtypes, Physiology and Pharmacology: New Ligands and Concepts in Schizophrenia

Dopamine Receptor Subtypes, Physiology and Pharmacology: New Ligands and Concepts in Schizophrenia

Intrinsic Connectivity Patterns of Task-Defined Brain Networks Allow Individual Prediction of Cognitive Symptom Dimension of Schizophrenia and Are Linked to Molecular Architecture

TAAR1-Dependent and -Independent Actions of Tyramine in Interaction With Glutamate Underlie Central Effects of Monoamine Oxidase Inhibition

Contact Info

Product

Resources

About