trifluoperazine / Generic mfg. - LARVOL DELTA

Infectious, inflammatory, and clinical outcomes among patients prescribed trifluoperazine or amoxapine: a retrospective cohort study using real-world data. (PubMed, Front Med (Lausanne)) - "Patients prescribed TFP, AXPN, fluoxetine, or no antidepressants/antipsychotics (general control) were assigned to mutually exclusive cohorts. These exploratory findings identify potential signals linking TFP and AXPN to infection susceptibility. Given the study design, these observations are hypothesis-generating and require confirmation in future prospective studies."

Clinical data • Journal • Real-world evidence • Retrospective data • CNS Disorders • Critical care • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • Septic Shock • CRP

Neurobiology Beyond Neurotransmitters: Structural Brain Pathology as a Substrate for Treatment-Resistant Psychosis — Two Rare Case Reports (WFSBP 2026) - "Olanzapine 20 mg, Risperidone 8mg, Trifluoperazine 20mg, and Valproate failed — paranoia and disorganisation persisted...Levetiracetam 2g and Valproate 2g failed seizures; antipsychotics barely touched psychosis... Psychosis is not always a disease of synapses. Structural brain pathology — neurodevelopmental and neuroinflammatory — can independently drive treatment-resistant psychosis beyond pharmacological reach. Pharmacological failure here was mechanistic, not a matter of dose."

Case report • Clinical • CNS Disorders • Epilepsy • Psychiatry

Trifluoperazine exhibits broad-spectrum antiviral activity against arboviruses. (PubMed, Antimicrob Agents Chemother) - "Alleviation of TFP-induced ER stress by chemical chaperone 4PBA abolished the antiviral activity of the drug and rescued virus replication in cells and CHIKV mice model. The robust in vitro and in vivo efficacy of the drug against arboviruses highlights the potential for repurposing TFP as a broad-spectrum antiviral candidate and underscores the importance of ER stress as a therapeutic target."

Journal • Chikungunya • CNS Disorders • Dengue Fever • Hematological Disorders • Infectious Disease • EIF2A • EIF2S1

Molecular dynamics perspectives on annexin-mediated plasma membrane repair: From recruitment to membrane mechanics. (PubMed, Biochim Biophys Acta Biomembr) - "Membrane-active perturbants such as trifluoperazine further suppress repair by altering bilayer thickness, lipid packing, phosphatidylserine mobility, and annexin binding. These findings shift the question from whether annexins arrive to how protein-membrane states generate repair-relevant remodeling."

Journal • Review • ANXA3

Multi-ancestry Transcriptome-Wide Association Study (TWAS)-Informed Prioritization of Antipsychotic Metabolic Risk: Evaluation of GLP1R as a Shared Mechanistic Link. (PubMed, Cureus) - "Clozapine and olanzapine are especially effective for psychosis but carry high liability for weight gain, dyslipidemia, insulin resistance, and type 2 diabetes...Haloperidol decanoate showed a high burden driven partly by SLC2A4, but its directionality was frequently mixed or compensatory...Except for the enrichment-positive European ancestry findings for trifluoperazine and fluspirilene, the results are exploratory prioritization signals and do not establish drug-specific metabolic effects, causal mechanisms, or ancestry-specific treatment effects. Overall, this TWAS-informed analysis provides a hypothesis-generating framework for ancestry-aware metabolic monitoring and targeted validation studies."

Journal • Cardiovascular • CNS Disorders • Diabetes • Dyslipidemia • Metabolic Disorders • Psychiatry • Type 2 Diabetes Mellitus • PPARG • SLC2A4

Astrocyte-derived HMGB1 compromises the integrity of the blood-brain barrier through the CaM/CaMKII/AQP4 pathway and the protective function of trifluoperazine. (PubMed, Front Immunol) - "TFP binds to CaM and blocks the translocation of AQP4 to the plasma membrane, thereby alleviating HMGB1-mediated BBB disruption. Overall, our data indicate that TFP protects BBB integrity through the CaM-CaMKII-AQP4 axis and identifies this pathway as a promising therapeutic target for the clinical treatment of Japanese encephalitis and other central nervous system diseases."

Journal • CNS Disorders • Infectious Disease • HMGB1

Targeting the FAK-Calmodulin Axis to Block Mechanobiological Tissue Factor Decryption: A Novel "Thrombo-Protective" Strategy in Cancer-Associated Thrombosis (ISTH 2026) - "Pharmacological interventions included the FAK inhibitor PF-562271 and the calmodulin antagonist Trifluoperazine (TFP). This offers a paradigm shift toward "Thrombo-protective Oncology," preventing thrombosis without the systemic bleeding risks associated with traditional anticoagulants. DOI*10.1016/j.rpth.2026.103773"

Breast Cancer • Oncology • Solid Tumor • Thrombosis

SREBP2-Driven Cholesterol Dependency Creates a Statin-Targetable Vulnerability in DMG (ISPNO 2026) - "Trifluoperazine (TFP) is an FDA-approved CNS-penetrant phenothiazine with reported effects on cancer metabolism. TFP exploits an intrinsic cholesterol dependency in DMG that is therapeutically targetable with statins. Patient tumors exhibit constitutively active SREBP2, and rescue experiments confirm cholesterol biosynthesis as the mechanistic target. Both TFP and atorvastatin are FDA-approved and extend survival as monotherapies in orthotopic models."

Brain Cancer • Diffuse Midline Glioma • Glioma • Solid Tumor

EXPRESS: Trifluoperazine reduces infarct size, restores neurovascular coupling and improves early outcomes in experimental acute ischemic stroke. (PubMed, J Cereb Blood Flow Metab) - "These findings suggest that transient modulation of astrocytic cytotoxic edema and vascular reactivity represents a viable strategy to improve early stroke outcomes. Given its established clinical use, TFP emerges as a promising candidate for therapeutic repurposing in AIS."

Journal • Cardiovascular • CNS Disorders • Ischemic stroke

Dysregulation of Non-Muscle Myosin IIA Assembly and Phosphorylation in S100A4 Null Mouse Lens. (PubMed, J Cell Physiol) - "Moreover, treatment of wild-type mouse lenses in ex-vivo with trifluoperazine, a known S100A4 inhibitor, induced lens opacification in association with increased insolubilization of S100A4, NMIIA and actin. Collectively, these findings demonstrate that S100A4 plays a critical role in regulating NMIIA activity and assembly, and maintaining actin cytoskeletal organization in the ocular lens, thereby contributing to lens transparency and homeostasis."

Journal • Preclinical • Cataract • Ophthalmology • S100A4

A membrane-permeable small molecule biosensor accesses intractable cells and animals without genetic manipulation. (PubMed, bioRxiv) - "The drug trifluoperazine, which binds only to the active conformation of calmodulin, was covalently linked to an environment-sensing merocyanine dye to create CaMero, a biosensor of calmodulin activation. Simple incubation of CaMero in the extracellular medium, or injection in the tail vein of mice, led to sensitive real time reporting of calmodulin activity. The dye underwent a 12-fold change in fluorescence intensity upon binding to activated calmodulin, revealing waves of activation in peristaltic intestine, localization and kinetics of calmodulin activation during serum stimulation in fibroblasts, and localized activation in the single-celled marine protist foraminifera."

Journal

Trifluoperazine induces ferroptosis in acute myeloid leukemia by suppressing the Nrf2/SLC7A11/GPX4 axis. (PubMed, Eur J Pharmacol) - "Acute myeloid leukemia (AML) remains a therapeutic challenge due to high relapse rates and limited treatment options. Importantly, TFP synergized with venetoclax, a standard AML therapy, to enhance antileukemic efficacy both in vitro and in vivo. Collectively, our findings identify TFP as a potent ferroptosis inducer in AML and suggest its potential as a repurposed therapeutic agent, either as monotherapy or in combination with venetoclax."

Journal • Acute Myelogenous Leukemia • CNS Disorders • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • GPX4 • SLC7A11

A phenothiazine analog, PTF, suppresses breast cancer growth by inhibiting YAP signaling. (PubMed, Eur J Pharm Sci) - "Compared with its precursor trifluoperazine, PTF exhibited markedly improved efficacy in inhibiting the proliferation of MCF-7 and MDA-MB-231 breast cancer cells, while sparing non-tumorigenic mammary epithelial cells (H184B5F/M10), which showed minimal sensitivity to the compound...Importantly, enforced expression of YAP attenuated PTF-induced cytotoxic effects, whereas blocking proteasomal function prevented PTF-driven degradation of YAP, implying that YAP destabilization contributes to the cytotoxic mechanism. Collectively, these results identify PTF as a potential therapeutic lead for breast cancer, acting through coordinated induction of apoptosis and autophagy, disruption of oncogenic signaling networks, and modulation of YAP protein stability."

Journal • Breast Cancer • CNS Disorders • Oncology • Oral Cancer • Psychiatry • Solid Tumor • MCL1 • YAP1

The role of type IV pilus in the interaction of Neisseria gonorrhoeae with a corneal epithelium tissue model. (PubMed, Infect Immun) - "The testing of trifluoperazine, a drug that induces pilus retraction, on infected corneal tissue models showed that the drug strongly diminished the number of adherent gonococci only when applied simultaneously with bacteria, and not when bacteria were allowed to form microcolonies on the tissue surface. Our work describes, for the first time, hTCEpi-based corneal epithelium tissue models as a useful tool for investigating N. gonorrhoeae infection, with potential for application in high-throughput studies and drug screening."

Journal • Infectious Disease • Ocular Inflammation • Oncology • Ophthalmology • CXCL8 • IL6 • TNFA

ROS-Responsive Trifluoperazine Prodrug Nanoparticles and Mesenchymal Stem Cell Exosomes Synergistically Modulate Astrocyte Phenotype for Spinal Cord Injury Repair. (PubMed, ACS Appl Mater Interfaces) - "In a murine SCI model, combined treatment with hUCMSC-Exos and TFP-ROS Nano outperformed each monotherapy: treated animals showed greater motor recovery by Basso Mouse Scale scores and better preservation of spinal cord architecture, with reduced tissue necrosis and maintained structural integrity. Together, these results suggest that the TFP-ROS Nano, especially when used synergistically with hUCMSC-Exos, provides a promising strategy to alleviate astrocytic edema and promote neuro-regeneration after SCI."

Journal • CNS Disorders • Orthopedics • AQP4

Trifluoperazine upregulates ACSS2-related autophagy and promotes cerebral cognitive function in rats after sleep deprivation. (PubMed, iScience) - "Our results showed that TFP administration in rats inhibited CaM protein following SD by upregulating ACSS2 protein expression, thereby improving ACSS2-related autophagy and alleviating cognitive function impairment. Consequently, this treatment may promote cerebral cognitive function recovery after SD."

Journal • Preclinical • Cardiovascular • Ischemic stroke • ACSS2

Trifluoperazine causes mast cell apoptosis through a secretory granule-mediated pathway. (PubMed, Cell Death Discov) - "Overall, these findings introduce trifluoperazine as a novel anti-mast cell agent that induces cell death through granule permeabilization. Trifluoperazine may thus be evaluated for therapeutic intervention to ameliorate mast cell-mediated detrimental effects."

Journal • CNS Disorders

Amelioration of gentamicin-induced acute kidney injury by trifluoperazine: in vivo mechanistic insights. (PubMed, Sci Rep) - No abstract available

Journal • Preclinical • Acute Kidney Injury • Nephrology • Renal Disease

Treating hearts and minds: adverse cardiovascular effects of psychiatric medications. (PubMed, Ther Adv Drug Saf) - "Increasing QT dispersion and induction of Brugada phenotype, both associated with serious cardiac arrhythmias and sudden death, can occur with certain antipsychotics (e.g. trifluoperazine), certain TCAs (e.g. amitriptyline), certain SSRIs (e.g. fluoxetine), methylphenidate and particular mood stabilisers (e.g. lithium)...It is important to note that pharmacokinetic drug-drug interactions, such as inhibition of the cytochrome P450 (CYP450) system, can affect the pharmacodynamic profile of psychiatric medications, thereby increasing the risk of their associated adverse cardiovascular effects. By understanding the main adverse cardiovascular effects of psychiatric medications and prescribing appropriately, clinicians can reduce potential harm in patients with SMI."

Journal • Review • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • Cardiomyopathy • Cardiovascular • CNS Disorders • Hypertension • Hypotension • Inflammation • Metabolic Disorders • Psychiatry

Novel 8-trifluoromethylquinobenzothiazines-Synthesis and Evaluation for Antiproliferative and Antibacterial Activity. (PubMed, Pharmaceuticals (Basel)) - "Objectives: The present study aimed to develop an efficient synthesis of 8-trifluoromethylquinobenzothiazines and to evaluate the anticancer and antibacterial potential of their N-substituted analogues inspired by triflupromazine, trifluoperazine, and fluphenazine. The obtained results identify 8-trifluoromethylquinobenzothiazines as a promising class of multifunctional compounds. Selected derivatives combine anticancer activity with acceptable selectivity or display potent antibacterial effects against clinically relevant Gram-positive pathogens."

Journal • Infectious Disease • Oncology • Pancreatic Cancer • Solid Tumor

First-generation antipsychotic shortages in the United States: Utilization and switching patterns. (PubMed, Explor Res Clin Soc Pharm) - "Most were receiving haloperidol (n = 52,344, 54.5%) and perphenazine (n = 16,966, 17.7%). Switching was common among individuals receiving thiothixene (32.8%), trifluoperazine (55.2%), and molindone (100%). Time to first switch ranged from 22 (standard deviation [SD]: 21) to 103 (SD: 66) days. Shortages of FGAs may influence patients' switching to other agents, including second generation antipsychotics."

Journal • CNS Disorders

Ubiquitin-Specific Proteases in Breast Cancer: Unraveling Oncogenic Roles and Therapeutic Opportunities. (PubMed, DNA Cell Biol) - "Pharmacological inhibitors of specific USPs, such as pimozide, trifluoperazine, rottlerin, 6-thioguanine, and costunolide, are highlighted for their potential to inhibit proliferation, metastasis, induce apoptosis, and circumvent therapy resistance across breast cancer subtypes (triple-negative and HER-2 positive). The review highlights the complex and often contradictory roles of USPs in breast cancer and points to the immense promise of targeting these enzymes to develop new and efficacious anticancer therapies."

Journal • Review • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • Triple Negative Breast Cancer • HER-2

Repurposing trifluoperazine as a potential therapeutic agent for ovarian cancer: mechanistic insight via SRC/PI3K/AKT signaling pathway inhibition. (PubMed, J Ovarian Res) - No abstract available

Journal • Oncology • Ovarian Cancer • Solid Tumor

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