An evaluation of lumateperone tosylate for the treatment of schizophrenia

Vyas, Pankhuri; Hwang, Brian Jaeho; Brašić, James Robert

doi:10.1080/14656566.2019.1695778

Cited by 25 publications

(65 citation statements)

References 28 publications

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“…It is possible for instance to separate β-arrestin mediated signals using biased D1 agonists ( Urs et al., 2011 ; Gray et al., 2018 ). Several recent contributions are available on this matter ( Vyas et al., 2020 ). The potential therapeutic applications of biased D2 ligands to new SCZ therapies, has fuelled new interest on D2S vs. D2L or cAMP independent intracellular pathways, looking for agents with less motor side effects.…”

Section: Section 3 Dr Ligands and Scz Therapies The New Wave Of Ligmentioning

confidence: 99%

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

Martel¹,

McArthur²

2020

Front. Pharmacol.

169

125

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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.

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Section: Section 3 Dr Ligands and Scz Therapies The New Wave Of Ligmentioning

confidence: 99%

“…(Abi-Dargham, 2020) Pharmacology Lumateperone D1 and D2-like antipsychotic profile./Cariprazine new data. (Vyas et al, 2020;Periclou et al, 2020)…”

Section: Cognitivementioning

confidence: 99%

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

Martel¹,

McArthur²

2020

Front. Pharmacol.

169

125

View full text Add to dashboard Cite

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“…Brexpiprazole, for instance, exhibits low risk of D2 receptor sensitization, is well-tolerated, and has low side effects in patients with schizophrenia Moreover, it may have a lower risk for producing rebound symptoms associated with D2 receptor and 5-HT 2A receptor sensitization when switching from other antipsychotics such as risperidone [ 52 , 53 ]. The most recently approved, first-in-class antipsychotic—lumateperone—combines the synergy of the drug’s affinity for 5-HT 2A receptors at low doses, dose-dependent presynaptic D2 receptors agonism, postsynaptic D2 antagonism, and selectivity to mesolimbic and mesocortical areas for a wide range of symptoms associated with schizophrenia [ 54 ].…”

Section: Dopaminergic Receptorsmentioning

confidence: 99%

The Role of G Protein-Coupled Receptors (GPCRs) and Calcium Signaling in Schizophrenia. Focus on GPCRs Activated by Neurotransmitters and Chemokines

Boczek

Mackiewicz

Sobolczyk

et al. 2021

Cells

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Schizophrenia is a common debilitating disease characterized by continuous or relapsing episodes of psychosis. Although the molecular mechanisms underlying this psychiatric illness remain incompletely understood, a growing body of clinical, pharmacological, and genetic evidence suggests that G protein-coupled receptors (GPCRs) play a critical role in disease development, progression, and treatment. This pivotal role is further highlighted by the fact that GPCRs are the most common targets for antipsychotic drugs. The GPCRs activation evokes slow synaptic transmission through several downstream pathways, many of them engaging intracellular Ca2+ mobilization. Dysfunctions of the neurotransmitter systems involving the action of GPCRs in the frontal and limbic-related regions are likely to underly the complex picture that includes the whole spectrum of positive and negative schizophrenia symptoms. Therefore, the progress in our understanding of GPCRs function in the control of brain cognitive functions is expected to open new avenues for selective drug development. In this paper, we review and synthesize the recent data regarding the contribution of neurotransmitter-GPCRs signaling to schizophrenia symptomology.

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“…In the liver, CYP3A4 leads to the formation of the last 2 active metabolites: IC200161 and IC200565 via dealkylation. 10,14 The half-lives of each of the active metabolites, respectively, are 10.8, 2.3, and 15.5 hours, with an average T max of 1.5 hours. 7 Radioactive doses of lumateperone were recovered in the urine and feces (58% and 29%, respectively).…”

Section: Pharmacokineticsmentioning

confidence: 99%

“…Steady state is achieved in about 5 days, and the half-life is 13 to 21 hours. [13][14][15] Ingestion of a high-fat meal leads to an approximate decrease in C max of 33%. Because gastrointestinal (GI) effects were seen in clinical trials, the lower C max when taking it with food may be beneficial in decreasing GI effects.…”

Section: Pharmacokineticsmentioning

confidence: 99%

Lumateperone: A Novel Antipsychotic for Schizophrenia

et al. 2020

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Objective: To provide a concise review of the new Food and Drug Administration (FDA)-approved antipsychotic, lumateperone, for use in schizophrenia. Data Sources: A literature search of PubMed was performed (January 2000 to May 2020) using the following key terms: lumateperone, Caplyta, and ITI-007. Abstracts from conferences, review articles, clinical trials, and drug monographs were reviewed. Study Selection and Data Extraction: Relevant English-language monographs and studies conducted in humans were considered. Data Synthesis: Lumateperone was FDA approved for the treatment of schizophrenia in December 2019 based on 2 published randomized, double-blind, placebo-controlled trials. Lumateperone’s pharmacology is consistent with that of other second-generation antipsychotics in that it has a higher affinity for the serotonin (5-HT2A) receptors compared with dopamine (D2) receptors but with lower affinities for α-1 and histaminergic receptors. In addition, it serves as a presynaptic dopamine partial agonist, serotonin reuptake inhibitor, and an indirect modulator of glutamatergic systems. Based on the 4-week clinical trials, lumateperone was well tolerated. Most common treatment-emergent adverse events were headache, somnolence, and dizziness. Relevance to Patient Care and Clinical Practice: At this time, lumateperone had a statistically significant reduction in Positive and Negative Syndrome Scale when compared with placebo and was not significantly associated with the extrapyramidal symptoms (EPS) and metabolic adverse effects commonly seen with other antipsychotics. Conclusions: Lumateperone has the potential to benefit individuals with schizophrenia who are intolerant to the EPSs or metabolic adverse effects of other antipsychotics. However, further head-to-head trials with commercially available antipsychotics are still required to assist in establishing its role in treatment.

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An evaluation of lumateperone tosylate for the treatment of schizophrenia

Cited by 25 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

The Role of G Protein-Coupled Receptors (GPCRs) and Calcium Signaling in Schizophrenia. Focus on GPCRs Activated by Neurotransmitters and Chemokines

Lumateperone: A Novel Antipsychotic for Schizophrenia

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