trifluoperazine / Generic mfg. - LARVOL DELTA

First-in-class small molecule calmodulin pathway modulators attenuate excess p53 activity and correct erythropoietic defects in models of diamond-blackfan anemia (DBA) (ASH 2025) - "2012) have demonstrated that calmodulin (CaM) inhibitors, including the FDA-approvedanti-psychotic trifluoperazine (TFP), improve anemia in multiple models of DBA by reducing activation ofp53 targets...FTX-1 and FTX-2 significantly rescuedhemoglobin levels at doses of 0.1 µM and 0.001 µM (p < 0.05 - <0.0001), respectively, compared to thepositive control fluphenazine at 10 µM (p < 0.05 - <0.01). Lastly, 1 µM FTX-1 was effective in restoringerythroid development by increasing the BFU-E and CFU-E colonies in RPS19 DBA patient-derived HSPCscompared to vehicle (adjusted p-value < 0.05) as assessed using a colony formation assay. FTX-2 iscurrently being explored in toxicology and safety pharmacology studies in support of an InvestigationalNew Drug (IND) application, with first-in-human studies anticipated in 2026."

Anemia • Aplastic Anemia • Bone Marrow Transplantation • CNS Disorders • Genetic Disorders • Hematological Disorders • CD34 • CDKN1A • DRD2 • RPL11 • RPL5 • RPS29

Neuroleptic Malignant Syndrome on Chronic Trifluoperazine Therapy: A Diagnostic Dilemma. (PubMed, Clin Case Rep) - "Neuroleptic malignant syndrome (NMS) is a rare, life-threatening reaction to antipsychotic medication. The patient's condition improved following supportive care, administration of bromocriptine, and lorazepam. This case highlights the diagnostic challenges of NMS in patients on a stable antipsychotic regimen and underscores the importance of early recognition, particularly after excluding infectious etiologies."

Journal • CNS Disorders • Infectious Disease • Septic Shock

Second generation repurposing of phenothiazine antipsychotic drugs as antifungal lead molecules via optimization of phenoxazine derivatives. (PubMed, Eur J Med Chem) - "Herein, we describe the repurposing and optimization of a series of phenoxazine analogs of the antipsychotic drugs fluphenazine and trifluoperazine as antifungals. In addition, the POZ analogs displayed reduced affinities towards serotonin and dopamine receptors compared to trifluoperazine. However, potent and moderately selective POZ analog 61 failed to demonstrate efficacy in a mouse model of cryptococcosis, demonstrating the need for further optimization."

Journal • CNS Disorders • Infectious Disease • GDF15

Ferroptosis in Oral Cancer: Mechanistic Insights and Clinical Prospects. (PubMed, Cells) - "Preclinical studies highlight the promise of small-molecule inhibitors, repurposed agents (e.g., sorafenib, artesunate, trifluoperazine), natural compounds (e.g., piperlongumine, Evodia lepta, quercetin), and nanomedicine platforms for targeted ferroptosis induction. Future research should focus on developing pharmacologically viable GPX4 inhibitors, refining biomarker-driven patient stratification, and designing multimodal regimens that combine ferroptosis induction with standard therapies while preserving immune and tissue integrity. Ferroptosis therefore represents both a mechanistic framework and a translational opportunity to reshape oral oncology and broader oral disease management."

IO biomarker • Journal • Review • Dental Disorders • Gene Therapies • Head and Neck Cancer • Infectious Disease • Oncology • Oral Cancer • Periodontitis • Solid Tumor • Squamous Cell Carcinoma • ACSL4 • AIFM2 • GPX4 • PER1 • SLC7A11

Neurological risk and protective associations of amoxapine and trifluoperazine: Retrospective cohort analysis from real-world data (Neuroscience 2025) - "Grant Support Clinical and Translational Science Award (UL1 TR001439) from the National Center for Advancing Translational Sciences, National Institutes of Health Trifluoperazine (TFP) and amoxapine (AXPN) are FDA-approved psychotropic medications with established central nervous system activity. Overall findings suggest a significantly lowered risk of mild cognitive impairment and restless leg syndrome for TFP compared to fluoxetine, while AXPN and fluoxetine showed no significant differences. The findings suggest potential neurological effects of TFP and support the need for further investigation into its repurposing potential for neuroprotection."

Real-world • Real-world evidence • Retrospective data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Epilepsy • Mental Retardation • Movement Disorders • Parkinson's Disease • Psychiatry • Restless Legs Syndrome • Sleep Disorder

Rice phospholipase C4 enhances Ca²⁺ and ROS bursts during effector-triggered immunity leading to ferroptotic cell death. (PubMed, Plant Commun) - "The Ca2+ chelator ethylene glycol-bis(2-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) significantly inhibited Ca2+, ROS, and Fe3+ accumulation and HR-related cell death in rice, whereas the Ca2+ influx enhancers trifluoperazine hydrochloride (TFP) and asibenzolar-S-methyl (ASM) strongly induced Ca2+-mediated ferroptotic cell death. Additionally, OsPLC4 overexpression triggered cell death and immune responses in Arabidopsis plants. Collectively, our findings provide evidence that OsPLC4, as a downstream target of resistosome activation, sustains the co-elevation of Ca2+ and ROS levels during rice ETI and promotes Ca2+-mediated, lipid ROS-dependent ferroptotic cell death, establishing OsPLC4 as a key regulator of Ca2+-dependent plant immunity."

Journal • Infectious Disease

Optimization of intranasal trifluoperazine/SPION-leciplex thermosensitive organogel for depression therapy: Pharmacodynamic and pharmacokinetic comparison of magnet placement effects on brain versus nose. (PubMed, Eur J Pharm Biopharm) - "The SPION-loaded leciplex organogel significantly improved intranasal TFP delivery, enabling dose reduction and superior efficacy compared with oral therapy. Magnet placement was profound in directing drug distribution toward systemic circulation or brain, suggesting that the two approaches may be clinically tailored-"magnet on nose" for systemic delivery and "magnet on brain" for CNS targeting."

Journal • PK/PD data • CNS Disorders • Depression • Mood Disorders • Psychiatry

Mechanism-based inhibition of squalene epoxidase by phenothiazines for lipid metabolism disruption using repurposed antipsychotic drugs. (PubMed, Sci Rep) - "Six compounds-ethopropazine, periciazine, piperacetazine, dixyrazine, fluphenazine and trifluoperazine-were prioritized for detailed MD simulations and MM/PBSA evaluation. In vitro assays confirmed potent SQLE inhibition, with IC₅₀ values of 1.69 ± 0.06 µM, 1.55 ± 0.13 µM and 1.44 ± 0.04 µM, respectively; kinetic studies established competitive inhibition with Ki values of 0.65-0.69 µM. The strong correlation between computational predictions and experimental data underscores the effectiveness of our integrated approach and identifies ethopropazine, periciazine and piperacetazine as promising lead compounds for further optimization and pre-clinical development as SQLE inhibitors."

Journal • CNS Disorders • Metabolic Disorders

Interictal psychosis in late-onset temporal lobe epilepsy with coexisting hydrocephalus: a case report of diagnostic and therapeutic challenges (ECNP 2025) - "He was started on sertraline and quetiapine but poor adherence led to worsening. In July 2024, he was hospitalized for hostility,diagnosed with anxiety disorder, and discharged on mirtazapine and trifluoperazine, which he discontinued, leading to recurrent symptoms.During the 2025 admission, further evaluation was prompted by ongoing symptoms and a prior epilepsy diagnosis from 2022...Levetiracetam was increased to 1250 mg/day and risperidone 1 mg/day was initiated...While interictal psychosis appears most likely, the cognitive effects of hydrocephalus may also play a contributory role. Long-term follow-up is essential for diagnostic clarity and treatment guidance."

Case report • Clinical • CNS Disorders • Epilepsy • Insomnia • Mental Retardation • Psychiatry • Schizophrenia • Sleep Disorder • Ventriculomegaly

A case of treatment-resistant depression unresponsive to multiple antidepressants, antipsychotics, mood stabilizers, and electroconvulsive therapy is presented (ECNP 2025) - "He was started on fluoxetine 40 mg/day at an external center in early 2023...Due to lack of clinical improvement, olanzapine 2.5 mg/day and venlafaxine 75 mg/day were initiated, with the latter increased to 150 mg/day. His suicidal ideation and restlessness worsened, leading to further emergency admissions and multiple medication adjustments.The patient was subsequently treated with a series of psychotropic medications, including escitalopram (up to 20 mg/day), clonazepam, lorazepam, amisulpride, and clomipramine, in various combinations...He was hospitalized multiple times and underwent six sessions of ECT, without significant improvement.Later, his regimen was modified to include quetiapine (100 mg/day IR and up to 200 mg/day XR), trifluoperazine, and alprazolam...Mood stabilizers, including valproic acid 750 mg/day and lamotrigine up to 100 mg/day, were introduced, along with aripiprazole and continued quetiapine...In this patient, persistent suicidality, poor..."

Clinical • Bipolar Disorder • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Movement Disorders • Psychiatry • Suicidal Ideation

The PDGFBB-PDGFRβ pathway and Laminins in pericytes are involved in the temporal change of AQP4 polarity during Temporal Lobe Epilepsy Pathogenesis. (PubMed, eNeuro) - "Following pilocarpine-induced chronic TLE model establishment, AQP4 polarity and pericyte vascular coverage rapidly increased but later declined, reaching the lowest levels in epileptic animals. Trifluoperazine prevented AQP4 redistribution, reduced seizure duration, and alleviated brain edema in PTZ-induced TLE mouse model...We further identify laminins and PDGF-BB as pericyte-derived molecules that may help maintain AQP4 polarity. These findings highlight pericyte-astrocyte interactions as potential therapeutic targets for delaying or reducing epileptogenesis, offering novel insight into mechanisms that underlie TLE and new avenues for intervention."

Journal • CNS Disorders • Epilepsy • LAMA1 • LAMA2 • PDGFB • PDGFRB

Trifluoperazine, an Antipsychotic Drug, Inhibits Viability of Cells Derived From SEGA and Cortical Tubers Cultured In Vitro. (PubMed, J Neurochem) - "Combination studies with rapamycin were conducted to evaluate their joint effects on cell viability and autophagy abnormalities, especially in SEGA-derived cells from rapamycin-resistant patients. Trifluoperazine appears promising as a treatment for TSC. However, further research is crucial to confirm its therapeutic benefits and safety profile in TSC patients, representing a significant direction for future TSC management studies."

Journal • Preclinical • Astrocytoma • Brain Cancer • CNS Disorders • Oncology • Solid Tumor • Subependymal Giant Cell Astrocytoma

Use of TLC and Computational Methods to Determine Lipophilicity Parameters of Selected Neuroleptics: Comparison of Experimental and Theoretical Studies. (PubMed, Pharmaceuticals (Basel)) - "Aim: Taking into account the importance of this parameter, we aimed to assess and compare the utility of a hybrid procedure based on calculation methods and an experimental one for rapid and simple estimation of the lipophilicity of selected neuroleptics such as fluphenazine, triflupromazine, trifluoperazine, flupentixol and zuclopenthixol and their potential new derivatives. Our results provide a confident proposal of optimal chromatographic conditions to experimentally determine the lipophilicity of neuroleptic drugs, including new derivatives. Additionally, for the first time, the paper shows the application of selected topological indices in determining lipophilicity factors and other ADMET parameters of neuroleptics and, in the future, the newly synthesized quinoline derivatives of the studied compounds."

Journal

The Combination of USP24-i-101-Astemizole Sensitizes the Cytotoxicity of Taxol and Gefitinib in Drug-Resistant Lung Cancer (IASLC-WCLC 2025) - "Introduction : Cancer is one of the major causes of death worldwide. Conclusions : In this study, we combined global USP24-interacting proteins, gene expression profiles from TCGA and lung cancer drug sensitive and resistant cells, along with clinical survival rate to screen for drug repurposing. Several approved clinical drugs, including 15d-PGJ2, Trifluoperazine, 1,4-Chrysenequinone and Astemizole, were found to inhibit chemotherapy-induced and target therapy-induced cancer drug resistance."

Lung Cancer • Oncology • Solid Tumor • EGFR • FEN1 • KRAS • PIAS4

The Future of Oncology in Psychiatric Medications. (PubMed, J Clin Med) - "The anticancer potential of psychiatric drugs seems to be extremely broad, and the most extensive anticancer literature has been reported on antidepressants (fluoxetine, amitriptyline, imipramine, mirtazapine, and St John's Wort) and antipsychotics (chlorpromazine, pimozide, thioridazine, and trifluoperazine)...Among antidementia drugs, memantine has documented anticancer effects, while there is limited evidence for galantamine. Of the new psychiatric substances, the antipsychotic drug brexpiprazole and the antidepressant vortioxetine have a very interesting body of literature regarding glioblastoma, based on in vitro and in vivo animal survival studies...The anticancer properties of psychiatric drugs may prove particularly useful in the period between chemotherapy and radiotherapy sessions to maintain the tumor-inhibitory effect. While further research is necessary to elucidate the mechanisms, clinical implications, dose-dependence of the effect, and clear..."

Journal • Brain Cancer • CNS Disorders • Depression • Glioblastoma • Oncology • Psychiatry • Solid Tumor • BCL2 • CDKN1A • SIRT1

Phenothiazine Derivatives and Their Impact on the Apoptosis Processes: A Review. (PubMed, J Appl Toxicol) - "Chlorpromazine, fluphenazine, levomepromazine, mepazine, perphenazine, promazine, promethazine, thioridazine, trifluoperazine, and trifluoperazine analog (3dc) more often induce apoptosis in cancer cell lines, human hepatocytes, and lymphocytes, and the final effect depends on the type and concentration of drug used, the type of cell line, and the methodology used. The obtained results allow for a better understanding of the biological action of phenothiazine derivatives and will help reposition this group of drugs to cancer treatment, resulting in faster, safer, easier, and cheaper therapy."

Journal • Review • Bipolar Disorder • CNS Disorders • Mood Disorders • Oncology • Psychiatry • Schizophrenia

Considerations for Augmenting Aripiprazole Long-Acting Injectables with Other Antipsychotics: A Mini-Review. (PubMed, Diseases) - "Current literature on Ki values indicates that fluphenazine, pimozide, thiothixene, trifluoperazine, and perphenazine bind more strongly to dopamine D2 receptors than aripiprazole...Additionally, the muscarinic effects of aripiprazole suggest the possibility of augmentation with clozapine or xanomeline-trospium, albeit the peer-reviewed literature on this was also limited. Overall, it is difficult to draw conclusions regarding best clinical practices for these scenarios, as the existing literature is contradictory. Nonetheless, the application of the dopamine and muscarinic pathway theories for schizophrenia opens venues for future research and consideration."

Journal • Review • CNS Disorders • Psychiatry • Schizophrenia • DRD2

The Mitochondrial Catastrophe Induced by NUPR1 Inhibitors as a Novel Strategy to Fight Against Cancer. (PubMed, Crit Rev Oncol Hematol) - "Applying a multidisciplinary approach, we identified the trifluoperazine-derived compound ZZW-115 with a remarkable efficacy...The inactivation of NUPR1 via ZZW-115 represents an innovative therapeutic strategy by exploiting specific vulnerabilities in tumor cells. By inducing severe mitochondrial dysfunction and disrupting energy metabolism, this approach selectively eliminates cancer cells, opening new avenues for the treatment of aggressive tumors resistant to conventional therapies."

Journal • Review • Metabolic Disorders • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • KRAS

Sexual dysfunctions related to use of antipsychotics: A protocol for a systematic review and meta-analysis. (PubMed, PLoS One) - "The antipsychotic medications of interest are amisulpride, aripiprazole, asenapine, brexpiprazole, cariprazine, chlorpromazine, clopenthixol, clozapine, droperidol, flupenthixol, fluphenazine, haloperidol, iloperidone, levomepromazine, loxapine, lurasidone, molindone, olanzapine, paliperidone, penfluridol, perphenazine, perazine, pimozide, prochlorperazine, quetiapine, risperidone, sertindole, sulpiride, thiothixene, thioridazine, trifluoperazine, ziprasidone, zuclopenthixol and zotepine. The Cochrane Risk of Bias tool and RoB 2.0 will be used to assess the risk of bias in studies. We will evaluate the quality of the evidence contributing to network estimates for the primary outcomes using the GRADE framework, and key factors that may affect the observed effects will be analysed for consistency across studies."

Journal • Retrospective data • CNS Disorders • Sexual Disorders • PRL

Therapeutic Targeting of Apoptosis, Autophagic Cell Death, Necroptosis, Pyroptosis, and Ferroptosis Pathways in Oral Squamous Cell Carcinoma: Molecular Mechanisms and Potential Strategies. (PubMed, Biomedicines) - "Additionally, the induction of ferroptosis via lipid peroxidation and glutathione peroxidase 4 (GPX4) inhibition offers a promising avenue for overcoming drug resistance, with agents such as quercetin and trifluoperazine exhibiting preclinical success. Integration of these therapeutic approaches may enhance the OSCC treatment efficacy, reduce chemoresistance, and provide novel prognostic biomarkers for clinical management. Future studies should focus on optimizing combinatorial strategies that effectively leverage these pathways to improve OSCC patient outcomes."

Journal • Review • Oncology • Oral Cancer • Squamous Cell Carcinoma • GPX4 • TNFA

Effect of Amitriptyline and Trifluoperazine on Patients With Functional Dyspepsia (clinicaltrials.gov) - P2/3 | N=150 | Recruiting | Sponsor: Md. Moktadirul Hoque Shuvo | Not yet recruiting ➔ Recruiting

Enrollment open • Dyspepsia

Trifluoperazine Nano-Level Assay in Pharmaceutical Formulation Using a Green and Simple Spectrofluorometric Approach Based on Ion Pairing With Erythrosine B: Application to Content Uniformity With Greenness and Blueness Evaluation. (PubMed, Luminescence) - "Finally, the greenness of the developed approach was assessed utilizing three advanced tools: the Eco-Scale, GAPI, and AGREE. In addition, the blueness of the approach was evaluated using a new tool called BAGI."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease • Psychiatry

Impact of Early Antipsychotic Prescription Choice on Weight Gain in the First 5 Years of Psychotic Illness: a Retrospective Cohort Study. (PubMed, Neurol Ther) - "Younger women were at elevated risk for weight gain as were people prescribed multiple antipsychotics in the 1st year. Some older antipsychotics associated with as much weight gain as the newer prescribed agents. More than 40% of people did not put on weight."

Journal • Retrospective data • CNS Disorders • Obesity • Psychiatry • Schizophrenia

Trifluoperazine Elevates Intracellular Ca2+ Levels and Locks Open the Store-Operated Calcium Entry Channels in Astrocytes. (PubMed, Glia) - "TFP induces a prolonged Ca2+ response, with distinct kinetics compared to other Ca2+ modulators such as TFLLR-NH2 (a Gαq-coupled GPCR agonist) and thapsigargin (a sacro/endoplasmic reticulum Ca2+-ATPase inhibitor). Together, these findings indicate that TFP elevates cytosolic Ca2+ levels by maintaining SOCE activation, offering novel insights into the molecular actions of this drug. TFP can be a pharmacological tool for SOCE research as it locks SOCE channels open."

Journal • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • STIM1

Effect of Amitriptyline and Trifluoperazine on Patients With Functional Dyspepsia (clinicaltrials.gov) - P2/3 | N=150 | Not yet recruiting | Sponsor: Md. Moktadirul Hoque Shuvo

New P2/3 trial • Dyspepsia