TY - JOUR

T1 - Ligands of the trace amine-associated receptors (TAARs): A new class of anxiolytics

AU - Alnefeesi, Y.

AU - Sukhanov, I.

AU - Gainetdinov, R.R.

N1 - Export Date: 19 October 2024 CODEN: PBBHA Адрес для корреспонденции: Gainetdinov, R.R.; Institute of Translational Biomedicine, Russian Federation; эл. почта: r.gainetdinov@spbu.ru Химические вещества/CAS: ulotaront, 1310426-33-5, 1310422-41-3; 4-(3-fluoro-2-methylphenyl)-4,5-dihydrooxazol-2-ylamine; Anti-Anxiety Agents; Ligands; Oxazoles; Receptors, G-Protein-Coupled; Trace amine-associated receptor 1; Trace Amine-Associated Receptors Сведения о финансировании: Russian Science Foundation, RSF, 19-75-30008-P Сведения о финансировании: Russian Science Foundation, RSF Текст о финансировании 1: This research was funded by the Russian Science Foundation grant 19-75-30008-P (to R.R.G.).

PY - 2024/9/1

Y1 - 2024/9/1

N2 - Most cases of anxiety are currently treated with either benzodiazepines or serotonin reuptake inhibitors. These drugs carry with them risks for a multitude of side effects, and patient compliance suffers for this reason. There is thus a need for novel anxiolytics, and among the most compelling prospects in this vein is the study of the TAARs. The anxiolytic potential of ulotaront, a full agonist at the human TAAR1, is currently being investigated in patients with generalized anxiety disorder. Irrespective of whether this compound succeeds in clinical trials, a growing body of preclinical literature underscores the relevance of modulating the TAARs in anxiety. Multiple behavioral paradigms show anxiolytic-like effects in rodents, possibly due to increased neurogenesis and plasticity, in addition to a panoply of interactions between the TAARs and other systems. Crucially, multiple lines of evidence suggest that the TAARs, particularly TAAR1, TAAR2, and TAAR5, are expressed in the extended amygdala and hippocampus. These regions are central in the actuation of anxiety, and are particularly susceptible to neurogenic and neuroplastic effects which the TAARs are now known to regulate. The TAARs also regulate the dopamine and serotonin systems, both of which are implicated in anxiety. Ligands of the TAARs may thus constitute a new class of anxiolytics. © 2024 Elsevier Inc.

AB - Most cases of anxiety are currently treated with either benzodiazepines or serotonin reuptake inhibitors. These drugs carry with them risks for a multitude of side effects, and patient compliance suffers for this reason. There is thus a need for novel anxiolytics, and among the most compelling prospects in this vein is the study of the TAARs. The anxiolytic potential of ulotaront, a full agonist at the human TAAR1, is currently being investigated in patients with generalized anxiety disorder. Irrespective of whether this compound succeeds in clinical trials, a growing body of preclinical literature underscores the relevance of modulating the TAARs in anxiety. Multiple behavioral paradigms show anxiolytic-like effects in rodents, possibly due to increased neurogenesis and plasticity, in addition to a panoply of interactions between the TAARs and other systems. Crucially, multiple lines of evidence suggest that the TAARs, particularly TAAR1, TAAR2, and TAAR5, are expressed in the extended amygdala and hippocampus. These regions are central in the actuation of anxiety, and are particularly susceptible to neurogenic and neuroplastic effects which the TAARs are now known to regulate. The TAARs also regulate the dopamine and serotonin systems, both of which are implicated in anxiety. Ligands of the TAARs may thus constitute a new class of anxiolytics. © 2024 Elsevier Inc.

KW - Anxiety

KW - Anxiolytic

KW - Dopamine

KW - GAD

KW - Neurogenesis

KW - Serotonin

KW - TAAR1

KW - TAAR2

KW - TAAR5

KW - Trace amine

KW - Ulotaront

KW - amine

KW - anxiolytic agent

KW - benzodiazepine derivative

KW - serotonin uptake inhibitor

KW - trace amine associated receptor

KW - ulotaront

KW - 4-(3-fluoro-2-methylphenyl)-4,5-dihydrooxazol-2-ylamine

KW - G protein coupled receptor

KW - ligand

KW - oxazole derivative

KW - Trace amine-associated receptor 1

KW - adult

KW - adverse drug reaction

KW - amygdala

KW - anxiety

KW - anxiety disorder

KW - controlled study

KW - drug interaction

KW - female

KW - generalized anxiety disorder

KW - hippocampus

KW - human

KW - male

KW - nervous system development

KW - patient compliance

KW - review

KW - serotoninergic system

KW - side effect

KW - animal

KW - drug therapy

KW - metabolism

KW - Animals

KW - Anti-Anxiety Agents

KW - Anxiety Disorders

KW - Humans

KW - Ligands

KW - Oxazoles

KW - Receptors, G-Protein-Coupled

KW - Trace Amine-Associated Receptors

UR - https://www.mendeley.com/catalogue/208d000f-1d73-3da5-9990-39b65b038ca8/

U2 - 10.1016/j.pbb.2024.173817

DO - 10.1016/j.pbb.2024.173817

M3 - статья

VL - 242

JO - Pharmacology, Biochemistry and Behavior

JF - Pharmacology, Biochemistry and Behavior

SN - 0091-3057

M1 - 173817

ER -