pimozide / Generic mfg. - LARVOL DELTA

Clinical trial to study the effect of an already authorized drug on othernpathologies by administering it to people with a recent diagnosis ofnschizophrenia. (clinicaltrialsregister.eu) - P2/3 | N=37 | Recruiting | Sponsor: Fundacion Para La Gestion De La Investigacion En Salud De Sevilla | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Psychiatry • Schizophrenia

Delusional Infestation: an Update on Patient Demographics, Clinical Features and Management through a Retrospective Case Series (AAD 2026) - "Pimozide was tried in 18 patients (24.3%), with only 7 (38.9%) reporting any improvement and 5 (27.8%) discontinuing it due to side effects. Second-generation antipsychotics were tried in 12 patients (16.2%), with only 2 (16.7%) reporting any improvement. These findings partially corroborate prior case series (2) and highlight the ongoing need for better management options."

Retrospective data • Bipolar Disorder • CNS Disorders • Depression • Mental Retardation • Mood Disorders

Sodium-glucose Co-transporter 2 (SGLT2) inhibitor dapagliflozin acutely activates cardiomyocyte HIF-1α signaling via succinate, a signaling metabolite. (PubMed, J Pharmacol Sci) - "Administration of pimozide, which is a succinyl-CoA:3-ketoacid CoA transferase (SCOT) inhibitor that inhibits ketone body metabolism, abolished dapagliflozin-elicited activation of HIF-1α signaling. These results, although not conclusive, can be plausibly explained if short-term Dapagliflozin treatment activates HIF-1α signaling in cardiomyocytes via ketone body-derived succinate. Our study raises the possibility that HIF-1α plays a role in the effects of SGLT2 inhibitors and highlights HIF-1α as a speculative target for future studies."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • HIF1A

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

Pimozide Reprograms the Ran GTPase-SCF Axis and Matrix Remodeling Pathways in Breast, Colorectal, and Pancreatic Cancer Models. (PubMed, Cancers (Basel)) - "Pimozide exerts anticancer effects through coordinated disruption of nucleocytoplasmic transport, proteostasis regulation, and matrix remodeling. These findings support the repositioning of pimozide as a multi-target anticancer agent and provide a mechanistic foundation for further translational investigation."

Journal • Preclinical • CNS Disorders • Colorectal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Targeted Protein Degradation • CUL1 • MMP2 • SKP2

Empagliflozin Attenuates Global Cerebral Ischemic Injury After Cardiac Arrest Through Enhancing Ketone Body Oxidative Metabolism in Rats. (PubMed, J Am Heart Assoc) - "Empagliflozin protects brain function after CA by enhancing oxidative metabolism of ketone body, and its underlying mechanism is associated with reducing neuroinflammation and improving mitochondrial energy metabolism. These findings suggest that empagliflozin may represent a novel therapeutic strategy for mitigating brain injury following CA."

Journal • Preclinical • Alzheimer's Disease • Cardiovascular • CNS Disorders • Cognitive Disorders • Oncology • Reperfusion Injury • Vascular Neurology • IL1B • TNFA

NeuroD1-USP1-MYCN axis drives tumor progression in neuroblastoma. (PubMed, J Transl Med) - "This study uncovered a novel oncogenic axis in neuroblastoma, where NeuroD1 transcriptionally upregulates USP1, promoting N-Myc stabilization and tumor progression. Furthermore, the findings highlight the therapeutic potential of repurposing Pimozide as a promising treatment strategy for this aggressive tumor subtype."

Journal • Neuroblastoma • Oncology • Solid Tumor • Targeted Protein Degradation • MYCN • NEUROD1 • USP1

Advancing Drug Repurposing for Rheumatoid Arthritis: Integrating Protein-Protein Interaction, Molecular Docking, and Dynamics Simulations for Targeted Therapeutic Approaches. (PubMed, Curr Issues Mol Biol) - " This multi-tiered computational workflow identified Rifampicin, Telmisartan, Danazol, and Pimozide as the most promising repurposing candidates. The key innovation of this study is this sequential funnel approach, which integrates large-scale network data with atomic-level simulation to prioritize high-confidence drug candidates for RA. In conclusion, this study highlights the potential of repurposing FDA-approved drugs to target key proteins involved in RA, offering a cost-effective and time-efficient strategy to discover new therapies."

Journal • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • AKT1 • IL1B • IL6 • STAT3 • TNFA

Pharmacokinetics of Inhibitors of Succinyl-CoA:3-Ketoacid CoA Transferase in Sprague-Dawley Rats, and the Effect of a High-Fat Diet. (PubMed, AAPS J) - "Both drugs possessed a high volume of distribution (Vd/F), but the oral clearance (CL/F) of PSSI-51 was much higher than that of pimozide, in line with earlier observations using rat microsomal experiments. The high-fat diet significantly reduced the oral CL and Vd of PMZ in both male and female rats, whereas no such effect was observed for PSSI-51."

Journal • PK/PD data • Preclinical • Diabetes • Genetic Disorders • Metabolic Disorders • Type 2 Diabetes Mellitus

Pharmacological Interventions for Excoriation Behaviors in Alzheimer's Disease: An Empty Systematic Review of Clinical Trials. (PubMed, Clin Neuropsychiatry) - "Two studies related to the topic were excluded because they were not clinical trials (a single case report and a case series), involving five patients treated with antipsychotics (risperidone, pimozide and thioridazine) and antidepressants (paroxetine). The absence of eligible studies suggests a gap in the literature and the lack of robust evidence on the pharmacological efficacy on these behavioral symptoms in this population. future clinical trials are needed to support specific therapeutic recommendations, since the evidence suggested by studies that are not clinical trials, evaluated in addition to the main objective of this review, is primary and limited."

Journal • Review • Alzheimer's Disease • CNS Disorders • Obsessive-Compulsive Disorder

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