Trifluoperazine versus placebo for schizophrenia

Koch, Kai; Mansi, Kamel; Haynes, Euan; Adams, Clive E

doi:10.1002/14651858.cd010226

Cited by 5 publications

(5 citation statements)

References 26 publications

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“…TFP is an effective antipsychotic drug for people with schizophrenia (34), acting by blocking central dopamine receptors. In early attempts to repurpose the drug, TFP and some of its derived compounds were noted to have anticancer effects in some (35)(36)(37)(38) but not all cancer models (39).…”

Section: Discussionmentioning

confidence: 99%

Ligand-based design identifies a potent NUPR1 inhibitor exerting anticancer activity via necroptosis

Santofimia‐Castaño¹,

Xia²,

Lan³

et al. 2019

Journal of Clinical Investigation

102

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Section: Discussionmentioning

confidence: 99%

Ligand-based design identifies a potent NUPR1 inhibitor exerting anticancer activity via necroptosis

Santofimia‐Castaño¹,

Xia²,

Lan³

et al. 2019

Journal of Clinical Investigation

102

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“…Current therapies for patients with DBA-including blood transfusions, corticosteroids, and HSC transplantation-have adverse effects. TFP and other phenothiazines are given to adults with schizophrenia and are well tolerated (39). One concern with reducing p53 activity in patients with DBA is that they are already at risk for certain cancers.…”

Section: Discussionmentioning

confidence: 99%

“…Together, these data indicate that CaM inhibitors from two different classes reduce the activity of p53 in a RPS19-deficient cell line model. The remainder of the studies focused on only one drug candidate, TFP, because it is an FDA-approved drug with a favorable safety profile and more than 60 years of use in patients (39).…”

Section: Cam Inhibitors Decrease P53 Activity In Human Cell Models Of...mentioning

confidence: 99%

Calmodulin inhibitors improve erythropoiesis in Diamond-Blackfan anemia

et al. 2020

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Diamond-Blackfan anemia (DBA) is a rare hematopoietic disease characterized by a block in red cell differentiation. Most DBA cases are caused by mutations in ribosomal proteins and characterized by higher than normal activity of the tumor suppressor p53. Higher p53 activity is thought to contribute to DBA phenotypes by inducing apoptosis during red blood cell differentiation. Currently, there are few therapies available for patients with DBA. We performed a chemical screen using zebrafish ribosomal small subunit protein 29 (rps29) mutant embryos that have a p53-dependent anemia and identified calmodulin inhibitors that rescued the phenotype. Our studies demonstrated that calmodulin inhibitors attenuated p53 protein amount and activity. Treatment with calmodulin inhibitors led to decreased p53 translation and accumulation but does not affect p53 stability. A U.S. Food and Drug Administration–approved calmodulin inhibitor, trifluoperazine, rescued hematopoietic phenotypes of DBA models in vivo in zebrafish and mouse models. In addition, trifluoperazine rescued these phenotypes in human CD34+ hematopoietic stem and progenitor cells. Erythroid differentiation was also improved in CD34+ cells isolated from a patient with DBA. This work uncovers a potential avenue of therapeutic development for patients with DBA.

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“…Trifluoperazine (TFP) is a clinical antipsychotic drug approved in 2001 and primarily used to treat schizophrenia caused by excess of dopamine [ 15 ]. TFP exerts an antipsychotic effect by blocking central dopamine and serotonin receptor in patients suffering from megalomania and hallucinations [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Repositioning of the antipsychotic drug TFP for sepsis treatment

Park

Lee

et al. 2019

J Mol Med

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Sepsis is a disease responsible for the death of almost all critical patients. Once infected by virus or bacteria, patients can die due to systemic inflammation within a short period of time. Cytokine storm plays an essential role in causing organ dysfunction and septic shock. Thus, inhibition of cytokine secretion is considered very important in sepsis therapy. In this study, we found that TFP, an antipsychotic drug mainly used to treat schizophrenia by suppressing dopamine secretion, inhibited cytokine release from activated immune cells both in vitro and in vivo. Trifluoperazine (TFP) decreased the levels of pro-inflammatory cytokines without altering their transcription level. In LPS-induced endotoxemia and cecal content injection (CCI) models, TFP intraperitoneal administration improved survival rate. Thus, TFP was considered to inhibit the secretion of proteins through a mechanism similar to that of W7, a calmodulin inhibitor. Finally, we confirmed that TFP treatment relieved organ damage by estimating the concentrations of aspartate transaminase (AST), alanine transaminase (ALT), and blood urea nitrogen (BUN) in the serum. Our findings were regarded as a new discovery of the function of TFP in treating sepsis patients. Key messages • TFP inhibits LPS-induced activation of DCs by suppressing pro-inflammatory cytokine. • Treatment of TFP increases survival of LPS-induced endotoxemia and CCI sepsis models. • TFP exerted a protective effect against tissue or organ damage in animal models. Electronic supplementary material The online version of this article (10.1007/s00109-019-01762-4) contains supplementary material, which is available to authorized users.

show abstract

Trifluoperazine versus placebo for schizophrenia

Cited by 5 publications

References 26 publications

Ligand-based design identifies a potent NUPR1 inhibitor exerting anticancer activity via necroptosis

Ligand-based design identifies a potent NUPR1 inhibitor exerting anticancer activity via necroptosis

Calmodulin inhibitors improve erythropoiesis in Diamond-Blackfan anemia

Repositioning of the antipsychotic drug TFP for sepsis treatment

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