Pimavanserin exhibits serotonin 5-HT2A receptor inverse agonism for Gαi1- and neutral antagonism for Gαq/11-proteins in human brain cortex

Muneta-Arrate, Itziar; Dı́ez-Alarcia, Rebeca; Horrillo, I.; Meana, J. Javier

doi:10.1016/j.euroneuro.2020.05.004

Cited by 30 publications

(27 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, for these receptor subtypes, biased agonism was demonstrated. This phenomenon results in activation of different signal pathways depending on ligand [ 24 , 264 , 265 , 266 ]. At the same time, for 5-HT 2C receptors, mRNA-editing resulting in the translation of various isoforms of receptor was shown [ 267 , 268 , 269 ].…”

Section: Discussionmentioning

confidence: 99%

The Implication of 5-HT Receptor Family Members in Aggression, Depression and Suicide: Similarity and Difference

Попова

Цыбко

Науменко

2022

IJMS

View full text Add to dashboard Cite

Being different multifactorial forms of psychopathology, aggression, depression and suicidal behavior, which is considered to be violent aggression directed against the self, have principal neurobiological links: preclinical and clinical evidence associates depression, aggression and suicidal behavior with dysregulation in central serotonergic (5-HT) neurotransmission. The implication of different types of 5-HT receptors in the genetic and epigenetic mechanisms of aggression, depression and suicidality has been well recognized. In this review, we consider and compare the orchestra of 5-HT receptors involved in these severe psychopathologies. Specifically, it concentrates on the role of 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3 and 5-HT7 receptors in the mechanisms underlying the predisposition to aggression, depression and suicidal behavior. The review provides converging lines of evidence that: (1) depression-related 5-HT receptors include those receptors with pro-depressive properties (5-HT2A, 5-HT3 and 5-HT7) as well as those providing an antidepressant effect (5-HT1A, 5-HT1B, 5-HT2C subtypes). (2) Aggression-related 5-HT receptors are identical to depression-related 5-HT receptors with the exception of 5-HT7 receptors. Activation of 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2C receptors attenuate aggressiveness, whereas agonists of 5-HT3 intensify aggressive behavior.

show abstract

Section: Discussionmentioning

confidence: 99%

The Implication of 5-HT Receptor Family Members in Aggression, Depression and Suicide: Similarity and Difference

Попова

Цыбко

Науменко

2022

IJMS

View full text Add to dashboard Cite

show abstract

“…This is of note due to the fact that it can be used as a precursor of serotonin in the human body. Thus, it is thought to help increase the levels of serotonin, which plays an important role in the treatment of depression in humans [24]. However, further exploration is needed to study the regulatory mechanism and function involved in fruit splitting.…”

Section: Discussionmentioning

confidence: 99%

Integrated Physiological and Metabolomic Analyses of the Effect of Potassium Fertilizer on Citrus Fruit Splitting

Jiao

Sha²,

Qiao-yun

2022

Plants

View full text Add to dashboard Cite

Potassium (K) nutrition plays a key role in alleviating a variety of peel disorders in tree fruit, but the effect of this nutrient on the physiological and metabolic profiles involved in the fruit splitting of citrus remains unclear. Three levels of K were used to treat citrus ‘Ehime Kashi 34’ (Citrus Nishinoka × C. Shiranui), a hybrid cultivar with fruit that easily split. The results showed that the roots of the treatment with K fertilizer increased the contents of calcium (Ca2+), nitrogen (N), and K in the skin and flesh, the fruit firmness ratio of the peel to the flesh, photosynthetic rate, stomatal conductance, and concentration of intercellular CO2. In contrast, it decreases the relative chlorophyll index and content of Ca2+ in the leaves. Simultaneously, 59 and 13 differentially expressed metabolites (DEMs) were detected in the peel and flesh, respectively, after treatment with K. Of them, five compounds were upregulated, including the synthesis of various amino acids in the peel and the accumulation of various glycoside metabolites in the flesh which were upregulated. The accumulation of levels of gibberellin and glycoside were downregulated. That could be the main reason why potassium alleviates fruit splitting.

show abstract

“…The discovery that 5-HT2A receptor inverse agonists have antipsychotic effects opened an alternative pathway for treating psychosis and drove the development of pimavanserin, a 5HT2A inverse agonist. Pimavanserin lacks dopamine receptor affinity but exhibits antipsychotic activity [ 65 ]. In 2016, the FDA and EMA approved pimavanserin for the treatment of psychosis in Parkinson’s disease.…”

Section: Serotonin In the Gi Tractmentioning

confidence: 99%

The Role of Serotonin Neurotransmission in Gastrointestinal Tract and Pharmacotherapy

Guzel

Mirowska‐Guzel

2022

Molecules

View full text Add to dashboard Cite

5-Hydroxytryptamine (5-HT, serotonin) is a neurotransmitter in both the central nervous system and peripheral structures, acting also as a hormone in platelets. Although its concentration in the gut covers >90% of all organism resources, serotonin is mainly known as a neurotransmitter that takes part in the pathology of mental diseases. Serotonin modulates not only CNS neurons, but also pain transmission and platelet aggregation. In the periphery, 5-HT influences muscle motility in the gut, bronchi, uterus, and vessels directly and through neurons. Serotonin synthesis starts from hydroxylation of orally delivered tryptophan, followed by decarboxylation. Serotonin acts via numerous types of receptors and clinically plays a role in several neural, mental, and other chronic disorders, such as migraine, carcinoid syndrome, and some dysfunctions of the alimentary system. 5-HT acts as a paracrine hormone and growth factor. 5-HT receptors in both the brain and gut are targets for drugs modifying serotonin neurotransmission. The aim of the present article is to review the 5-HT receptors in the gastrointestinal (GI) tract to determine the role of serotonin in GI physiology and pathology, including known GI diseases and the role of serotonin in GI pharmacotherapy.

show abstract

Pimavanserin exhibits serotonin 5-HT2A receptor inverse agonism for Gαi1- and neutral antagonism for Gαq/11-proteins in human brain cortex

Cited by 30 publications

References 26 publications

The Implication of 5-HT Receptor Family Members in Aggression, Depression and Suicide: Similarity and Difference

The Implication of 5-HT Receptor Family Members in Aggression, Depression and Suicide: Similarity and Difference

Integrated Physiological and Metabolomic Analyses of the Effect of Potassium Fertilizer on Citrus Fruit Splitting

The Role of Serotonin Neurotransmission in Gastrointestinal Tract and Pharmacotherapy

Contact Info

Product

Resources

About