pimozide / Generic mfg. - LARVOL DELTA

Drug Repurposing Screen Identifies Pimozide as a ROS-Inducing Therapy With Anti-Tumor Efficacy in HNSCC PDX Models. (PubMed, Cancer Sci) - "Notably, pimozide exhibited anti-tumor effects as a monotherapy and in combination with paclitaxel at clinically relevant doses. While tumor volume reduction in the combination group was not statistically greater than that in the monotherapy group, fluorescence immunohistochemistry revealed a marked decrease in undifferentiated tumor cells, indicating enhanced therapeutic effects of combination treatment. Taken together, these findings indicate that pimozide is a promising candidate for repurposing as a novel therapeutic agent against HNSCC."

Journal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • DRD2 • EGR1 • STAT3

QT interval prolongation in acute antipsychotic poisoning: systematic review and recommendations. (PubMed, Clin Toxicol (Phila)) - "Individual medication recommendations were made for amisulpride (15 articles), thioridazine (11 articles), ziprasidone (eight articles) and quetiapine (13 articles), whilst consensus statements based on limited data were made for acute ingestions of clozapine, haloperidol, iloperidone, pimozide, pipamperone, olanzapine and risperidone (14 articles in total). The QT Interval Prolongation in Clinical Toxicology Workgroup suggests the same approach for patients with overdoses of haloperidol, iloperidone, pipamperone and pimozide. The risk of torsade de pointes is likely overstated for acute antipsychotic medication overdose as a general class group, and concern should rather focus on a few specific medications."

Journal • CNS Disorders

ARPC2 Targeting Inhibition Progress the Proliferation Suppression of Acute Myeloid Leukemia through PI3K-AKT Pathway (ASH 2024) - "They could also suppress the PI3K and AKT proteins, which are the key proteins of PI3K/AKT pathway, and this consistent with GSEA analysis.Conclusion : High expression of ARPC2 is an independent adverse prognostic factor for AML patients. Benproperine phosphate and pimozide can inhibit the proliferation and promote apoptosis of AML cells by targeting ARPC2 through PI3K-AKT pathway, which may provide a new idea for the future targeted therapy of AML."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • ACTR2 • BCL2

Update on Pharmacology in Tourette's Disorder (AACAP 2025) - "There are only 3 pharmacological interventions FDA-approved for TD: pimozide, haloperidol, and aripiprazole, and as such, most treatments are used off-label...She will also describe recent trials that did not meet their primary end points (eg, deutetrabenazine, nabiximols), but may still hold promise for certain individuals/subgroups with TD... There is a great need for new medications for TD that are as effective for tics as antipsychotics, but without the potential short and long-term side effects associated with typical and atypical antipsychotics. Recently, new medications currently in Phase IIb and III trials are showing great promise!.TD, TICD, PPC"

CNS Disorders • Mental Retardation • Movement Disorders • Psychiatry • Tourette Syndrome

Pharmacogenetic Guidelines and Resources to Support Antidepressant and Antipsychotic Use in Child and Adolescent Psychiatry (AACAP 2025) - "The FDA categorizes drug-gene pairs by implications on therapeutic management, safety, or pharmacokinetics. If a patient has genotype results available, the CPIC and/or FDA currently provide assessments supporting the utility of PGx to inform the use of many antidepressants including es/citalopram (CYP2C19), fluvoxamine (CYP2D6), paroxetine (CYP2D6), sertraline (CYP2C19 and CYP2B6), TCAs (CYPC19 and/or CYP2D6), venlafaxine (CYP2D6), and vortioxetine (CYP2D6)...FDA labeling provides specific dosing based on CYP2D6 poor metabolizer genotypes for aripiprazole, brexpiprazole, iloperidone, pimozide, and thioridazine... CPIC and FDA resources are useful for identifying evidence-based PGx information for commonly used antidepressants and antipsychotics. PharmGKB and Sequence2Script support access to foundational literature and the clinical implementation of PGx results.PPC, ADP, APS"

Biomarker • Clinical • CNS Disorders • Psychiatry • CYP19A1 • CYP2C19 • HTR2A • SLC6A4

Role of Ubiquitin-specific Protease 1 in the Pathogenesis and Treatment of Adult T-Cell Leukemia. (PubMed, Anticancer Res) - "Our study supports the clinical potential of USP1 inhibitors as a novel therapy for ATL."

Journal • Adult T-Cell Leukemia-Lymphoma • Hematological Malignancies • Leukemia • Metabolic Disorders • Oncology • Targeted Protein Degradation • CTNNB1 • LDHA • MYC • PLK1 • USP1

Valbenazine for the Treatment of Chronic Motor or Vocal Tic Disorder (CMVTD). (PubMed, Cureus) - "The present report describes a pediatric patient with CMVTD who had previously failed multiple pharmacological treatments, including two Food and Drug Administration (FDA)-approved agents (pimozide, aripiprazole), guanfacine, psychotherapy, and novel compounds (lumateperone, cariprazine). This case illustrates a marked therapeutic response to valbenazine in a patient with CMVTD refractory to conventional and novel therapies. These observations highlight the potential role of vesicular monoamine transporter 2 (VMAT2) inhibition in tic disorders and also the need for further clinical study."

Journal • CNS Disorders • Otorhinolaryngology • Pediatrics • Psychiatry • Tic Disorders • Tourette Syndrome

Real-World Adverse Event Profile in Children and Adolescents With Tourette Syndrome Treated With Dopamine D2 Receptor Antagonists (D2RAs) Compared With Non-D2RAs (MDS Congress 2025) - "Background: D2RAs (aripiprazole/haloperidol/pimozide) are indicated for the treatment of TS. In a real-world health care setting, children with TS treated with D2RAs were more likely to experience multiple metabolic and neuropsychiatric AEs versus non-exposed individuals. These findings highlight the need for safer TS treatment options."

Adverse events • Clinical • Real-world • Real-world evidence • CNS Disorders • Depression • Dystonia • Movement Disorders • Psychiatry • Sleep Disorder • Suicidal Ideation • Tourette Syndrome

Increased Health Care Utilization in Children/Adolescents With Tourette Syndrome Treated With Dopamine D2 Receptor Antagonists: An Electronic Medical Records Database Analysis (MDS Congress 2025) - "Background: TS is a neurodevelopmental disorder characterized by motor/vocal tics, and D2RAs (aripiprazole, haloperidol, pimozide) are indicated for TS...Common first-month D2RAs were risperidone (40.3%), aripiprazole (30.4%), and haloperidol (6.5%)... These data highlight the high HCRU burden in children and adolescents with TS treated with D2RAs."

Clinical • HEOR • CNS Disorders • Movement Disorders • Psychiatry • Tourette Syndrome • DRD2

Effectiveness of 40-Session Repetitive Transcranial Magnetic Stimulation in Tourette Syndrome: A 6-Month Follow-Up Case Report. (PubMed, Turk Psikiyatri Derg) - "Pharmacological treatment included escitalopram (10 mg/day), followed sequentially by pimozide (4 mg/day), tetrabenazine (3*25 mg/day), and aripiprazole (10 mg/day). This report suggests that rTMS may be a promising alternative for TS patients with psychiatric comorbidities, particularly those who cannot tolerate medications or achieve sufficient symptom control through pharmacotherapy alone. Keywords: Tourette’s Syndrome, Repetitive Transcranial Magnetic Stimulation, Supplementary Motor Area."

Journal • CNS Disorders • Developmental Disorders • General Anxiety Disorder • Mood Disorders • Movement Disorders • Psychiatry • Tourette Syndrome

REPURPOSING PIMOZIDE TO REVERSE HEPATIC FIBROSIS VIA AMPK-YAP/TAZ SIGNALING IN HEPATIC STELLATE CELLS (AASLD 2025) - "Through a small molecule screen, we discovered that pimozide promotes HSC inactivation and ameliorates hepatic fibrosis. Mechanistically, our findings identify a novel cascade by which pimozide activates LKB1-AMPK to inhibit YAP/TAZ signaling in HSCs. These findings suggest that pimozide may be repurposed for the treatment of hepatic fibrosis."

CNS Disorders • Fibrosis • Hepatology • Immunology • Inflammation • Metabolic Dysfunction-Associated Steatohepatitis • STK11

Chemoselective Cu-Catalyzed Cross-Nucleophile Alkylarylation of Alkenes. (PubMed, ACS Catal) - "A scope of 37 examples is presented with structurally and electronically diverse alkyl, vinyl, and aryl coupling partners. The synthetic utility is demonstrated in the preparation of Pimozide and MCF-7 analogues."

Journal

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

TDP-43 proteinopathies and neurodegeneration: insights from Caenorhabditis elegans models. (PubMed, FEBS J) - "By employing its simplicity and genetic manipulability, we discuss how these models have helped identify chemical and genetic suppressors of TDP-43-induced phenotypes, including small molecules like Pimozide and the probiotic Lacticaseibacillus rhamnosus HA-114, now in clinical trials. This review underscores the translational value of C. elegans in unraveling the biochemical pathways and interactions in TDP-43 proteinopathies that perturb cellular physiology, potentially facilitating mechanism-based therapy development."

Journal • Review • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Huntington's Disease • Movement Disorders • Parkinson's Disease • Proteinopathy • TARDBP

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

Peroxisomal lipid metabolism inhibits Pimozide-induced cancer cell death by regulating ATP homeostasis. (PubMed, Oncogenesis) - "As key metabolic hubs interconnected with mitochondrial metabolism, peroxisomes support energy homeostasis, thereby preventing Pimozide-induced cell death. These findings underscore the importance of peroxisomes in maintaining mitochondrial morphology and cellular energy homeostasis, offering novel insights into the potential therapeutic applications of Pimozide in cancer treatment."

Journal • CNS Disorders • Metabolic Disorders • Oncology

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

Repurposed Antipsychotics as Potential Anticancer Agents: Clozapine Efficacy and Dopaminergic Pathways in Neuroblastoma and Glioblastoma. (PubMed, Life (Basel)) - "This study aimed to evaluate the potential anticancer effects of repurposed antipsychotic dopamine-targeting drugs (Clozapine, CLZ; Pimozide, PIM; Olanzapine, OLZ; and Risperidone, RIS) and antiemetic drugs (Domperidone, DOM; Droperidol, DRO) on neuroblastoma (SH-SY5Y) and glioblastoma (A172) cell lines, and to assess whether their efficacy is modulated by oxidative stress and DA synthesis. In summary, several of the repurposed antipsychotics demonstrated cytotoxic effects on central nervous system tumor cells, with CLZ showing the most promising activity, even under oxidative stress conditions. These findings support further investigation into dopamine-targeting drugs as potential therapeutic agents in neuro-oncology."

Journal • Brain Cancer • CNS Disorders • CNS Tumor • Glioblastoma • Neuroblastoma • Oncology • Solid Tumor

Identification of FDA-Approved Drugs That Inhibit SARS-CoV-2 and Human Norovirus Replication. (PubMed, Biol Pharm Bull) - "Among the hit compounds, 5 compounds (auranofin, endoxifen, netupitant, pimozide, and regorafenib) were selected for further analysis. Interestingly, 4 of them, except for auranofin, significantly suppressed human norovirus (HuNoV) replication in human intestinal organoids. In brief, we identified several FDA-approved drugs that inhibit SARS-CoV-2 and HuNoV replication, which warrant further investigation."

FDA event • Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Efficacy of Antipsychotic Treatment for Delusional Infestation: A Retrospective Cohort Study. (PubMed, J Cutan Med Surg) - "Amisulpride, followed by paliperidone and risperidone, emerged as the most effective treatments for DI, with the greatest reductions in symptom severity, confirming previous studies. The effect is significant over time."

Journal • Retrospective data • CNS Disorders • Dermatology • Mental Retardation • Psychiatry

HIGH MIR-202-5P EXPRESSION AT INITIAL DIAGNOSIS AS A PREDICTIVE BIOMARKER FOR TYROSINE KINASE INHIBITOR RESISTANCE IN CHRONIC MYELOID LEUKEMIA-- A RESULT FROM A NESTED CASE-CONTROL STUDY (EHA 2025) - "Baseline miR-202-5p overexpression robustly predicts TKI resistance in CML, supporting its clinical utility for risk stratification. Building on our earlier discovery of Pimozide's ability to reverse miR-202-5p-mediated resistance in vitro, these findings propose a precision medicine paradigm: miR-202-5p-guided selection for TKI-Pimozide combination therapy."

Biomarker • Clinical • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • CASP6 • STAT5 • STAT5AWqe

Development of a succinyl CoA:3-ketoacid CoA transferase inhibitor selective for peripheral tissues that improves glycemia in obesity. (PubMed, iScience) - "Importantly, PSSI-51 treatment improved glycemia in obese mice and demonstrated reduced brain accumulation compared to the diphenylbutylpiperidine pimozide. We propose that PSSI-51 can lay the foundation for optimizing a new class of brain-impermeable SCOT inhibitors for treating T2D."

Journal • CNS Disorders • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Stable 13C-glutamine Tracing Resolved Metabolomics for Cancer Metabolism Study. (PubMed, Bio Protoc) - "In addition, using this protocol, we also unveil previously unknown metabolic alterations in GBM cells following lysosome inhibition by the antipsychotic drug pimozide...• Distinguishes isomers of long-chain fatty acids, such as palmitoleic acid (16:1n-7) (cis-9-Hexadecenoic acid) and palmitelaidic acid (16:1n-7) (trans-9-Hexadecenoic acid), which share the exact same mass. • The method is utilized to investigate glutamine metabolism reprogramming in cancer cells following lysosome inhibition."

Journal • Brain Cancer • CNS Disorders • Glioblastoma • Oncology • Solid Tumor

Heads Up: A Potential Interplay Between Antipsychotic Medications Sickle Cell Trait and Priapism (APA 2025) - "He experienced priapism with aripiprazole, risperidone, paliperidone, olanzapine, and lurasidone. Despite switching to cariprazine, which has lower alpha-1 adrenergic antagonism, episodes of priapism persisted. The patient achieved partial psychiatric stabilization with a low dose of pimozide and valproate, and sildenafil was added as a preventive measure for priapism, resulting in no further episodes. Pimavanserin was not pursued due to its cost... Clinicians should be aware of this potential side effect and educate patients on the importance of reporting symptoms and seeking timely medical care. Further research is needed to clarify the mechanisms of priapism related to antipsychotic use, develop treatment protocols for managing psychosis in cases of recurrent priapism, and explore the relationship between sickle cell trait and antipsychotic-induced priapism."

Cardiovascular • CNS Disorders • Genetic Disorders • Hematological Disorders • Psychiatry • Schizophrenia • Sickle Cell Disease

Unsupervised Graph Clustering Reveals a Clinical Taxonomy of Antipsychotics (APA 2025) - "Cluster 1 contained Aripiprazole, Brexpiprazole, Cariprazine, Lurasidone, Sertindole, and Ziprasidone, and was characterized by an excellent side-effect profile but also with the lowest efficacy. Cluster 2 contained Chlorpromazine, Haloperidol, Loxapine, Molindone, Perphenazine, and Thiothixene, and showed strong efficacy in positive symptoms, but also had a high-risk for EPS, QTc prolongation and seizures. Cluster 3 contained Clozapine, Iloperidone, Olanzapine, Quetiapine, Thioridazine, and Zotepine, and showed strong overall efficacy but carried the highest risk for sedation and metabolic side effects. Cluster 4 contained Amisulpride, Asenapine, Paliperidone, Risperidone, and Sulpride, and showed excellent positive and negative symptom efficacy but carried the highest risk of hyperprolactinemia. Cluster 5 contained Flupentixol, Fluphenazine, Pimozide, and Trifluoperazine and showed the lowest efficacy with a high risk of causing EPS. Conclusion Despite traditional..."

Clinical • Anesthesia • CNS Disorders • Epilepsy • Hypotension • Psychiatry • Schizophrenia