pimozide / Generic mfg. - LARVOL DELTA

Adipocyte-derived β-hydroxybutyrate confers metabolic resilience in multiple myeloma. (PubMed, Nat Commun) - "Importantly, combining an AMPK activator (metformin) with an OXCT1 inhibitor (pimozide) or a NAT10 inhibitor (remodelin) shows synergistic anti-tumor activity in vivo. Our findings position adipocyte-derived β-OHB as a critical metabolic adaptor and highlight a potential combination therapy for MM."

Journal • Genetic Disorders • Hematological Malignancies • Multiple Myeloma • Obesity • Oncology • CDC37 • HMGCS2 • HSP90AA1 • IRF4 • OXCT1 • TRIM21

Virtual screening of Alpha-Aminoadipate Aminotransferase inhibitors from FDA approved drugs for Glutaric Acidemia Type I (SSIEM 2026) - "Conclusion Among the evaluated compounds, lomitapide and pimozide emerged as the most promising candidates, exhibiting both sustained binding stability during molecular dynamics simulations and the most favorable binding free energies under the MM/GBSA model. Further experimental studies are required to evaluate the inhibitory activity and therapeutic potential of these compounds in biochemical and cellular models."

CNS Disorders • Metabolic Disorders

COMBINED SECOND HARMONIC AND LINEAR LIGHT SCATTERING AS A TOOL FOR SOLUBILITY AND AGGREGATION SCREENING. (PubMed, Eur J Pharm Sci) - "LLS, which reports on particle size/number, detected precipitation onsets typically close to or below HPLC values and could resolve particle formation down to ∼0.1 µM for pimozide, substantially exceeding the sensitivity of standard nephelometric methods. SHS, which is sensitive to interfacial asymmetry and nonlinear susceptibility, often showed onsets and complex peak-drop-rise patterns that deviated from LLS, particularly for lopinavir, loratadine, and ritonavir, indicating structurally distinct, largely centrosymmetric drug-rich assemblies above the solubility limit. Orthogonal characterization by scanning electron microscopy, Capflex (capillary flow with a hydrophobic fluorescent tracer), and confocal fluorescence microscopy provided independent evidence for droplet-like or amorphous drug-rich domains that preceded bulk precipitation. Together, the results showed that combined SHS-LLS enabled highly sensitive detection of precipitation, while revealing..."

Journal

Pimozide Overdose-induced Extrapyramidal Symptoms Mimicking Neuroleptic Malignant Syndrome: A Case Report with Literature Review. (PubMed, Ann Afr Med) - "Fever resolved with antibiotics, and EPS improved with supportive care and levodopa-carbidopa. Differentiation relies on CPK levels and fever response. Supportive care and prolonged observation are critical for favorable outcomes."

Journal • CNS Disorders • Depression • Infectious Disease • Mood Disorders • Movement Disorders • Obsessive-Compulsive Disorder • Pneumonia • Psychiatry • Respiratory Diseases

Discovery of GPCR Antagonists with Potent In Vitro and In Vivo Macrofilaricidal Activity. (PubMed, J Med Chem) - "We explored repurposing human GPCR antagonists, including clemizole, pimozide, proroxan, and suloctidil, along with 45 rationally designed analogs for activity against Brugia pahangi and two Onchocerca species...Caenorhabditis elegans reverse genetics screen identified gar-3 and ser-7 as putative nematode targets of clemizole and its analogs. Clemizole, C-8, and S-17 represent promising leads for further optimization as antifilarial drugs."

Journal • Preclinical • Infectious Disease • GPRC6A

MLAC: MicroED-assisted ligand structure analysis in complexes and its application to hERG-ligand complexes. (PubMed, J Struct Biol) - "MicroED structures of representative hERG ligands-astemizole, pimozide, and E-4031-were determined at resolutions of 0.66-0.92 Å and then used for model fitting and refinement...Notably, MicroED frequently revealed structural polymorphs that provided alternative ligand conformations and helped resolve modeling ambiguities, including the chair-boat conformational variability of the piperidine ring and alternative ligand placements in the hERG-astemizole complex. Collectively, these findings support MLAC as a proof-of-concept framework that provides experimentally determined starting models to complement computational ligand-generation approaches."

Journal

High-throughput 3D modelling of medulloblastoma reveals a repurposed CNS drug targeting MYC-driven disease (ISPNO 2026) - "Pimozide also modestly enhanced sensitivity to vincristine, supporting its potential use in combination strategies. Importantly, the use of clinically approved, brain-penetrant compounds within a three-dimensional brain-relevant context enhances translational potential and supports rapid identification of candidate therapies that may reduce reliance on highly toxic treatments in paediatric medulloblastoma. In summary, we report a robust and scalable three-dimensional screening platform for medulloblastoma drug discovery and identify pimozide as a promising repurposed candidate for aggressive disease, warranting further preclinical evaluation alone and in combination with existing therapies."

Brain Cancer • Medulloblastoma • Solid Tumor • DRD2 • MYC

Pimozide Inhibits CatSper Activity, Impairs Hyperactivation and the Acrosome Reaction in Human Spermatozoa. (PubMed, Int J Mol Sci) - "Pimozide is an FDA approved drug known to block T-type calcium channels and which shares structural similarities with mibefradil, a proven antagonist of the CatSper channel. Experimental findings further support this, showing that pimozide inhibits CatSper activity, and impairs hyperactivation and the acrosome reaction in human spermatozoa. Overall, these results identify pimozide as a novel CatSper antagonist and propose a binding mode, offering a basis for the rational design of reversible, non-hormonal male contraceptives that target the CatSper channel."

Journal

Delusional parasitosis: 9-year experience from a psychodermatology unit. (PubMed, Actas Dermosifiliogr) - "Delusional parasitosis is an entity that dermatologists should consider in routine clinical practice. This condition represents a challenge for clinicians because of patients' poor therapeutic adherence and its complex multidisciplinary management."

Journal • CNS Disorders • Dermatology • Mental Retardation • Pruritus • Psychiatry • Restless Legs Syndrome

Treatment non-persistence in children and adolescents with Tourette syndrome newly treated with dopamine D2 receptor modulators. (PubMed, Front Psychiatry) - "Dopamine D2 receptor antagonists/partial agonists (D2RAs), including the US Food and Drug Administration-approved Tourette syndrome (TS) agents haloperidol, pimozide, and aripiprazole and other antipsychotics with dopamine D2 receptor-modulating properties, are prescribed for TS. Children and adolescents with TS newly treated with a D2RA showed substantial decline in documented D2RA medication records over follow-up and had higher recorded odds of AEs and HCRU rates than did those without D2RA exposure. These findings should be interpreted as associational rather than causal effects and may reflect residual confounding by indication, differential monitoring, and/or greater underlying disease severity/complexity in the treated cohort."

Journal • CNS Disorders • Movement Disorders • Pediatrics • Sleep Disorder • Tic Disorders • Tourette Syndrome • DRD2

Managing Dermatologic Delusional Disorders: A US Psychodermatology Perspective for Clinicians. (PubMed, CNS Drugs) - "However, over the past half a century, several medications with antipsychotic properties have been found to be effective in the treatment of these conditions in the USA, especially pimozide and risperidone. Therefore, this paper highlights pragmatic engagement strategies, pharmacotherapy principles, essential safety monitoring, and research priorities. Experience-based recommendations are clearly labeled as such."

Journal • Review • CNS Disorders • Dermatology • Psychiatry

Pharmaco-Epigenomic response of Pimozide is mediated through miR-2909. (PubMed, Integr Biol (Camb)) - "This integrative approach-combining molecular biology, gene expression profiling, and epigenetic analysis-provides new biological insight into the repurposing of psychiatric drugs for cancer therapy. Our findings highlight the therapeutic potential of targeting microRNA-epigenetic interactions and suggest a broader applicability of integrating pharmacology with systems biology to uncover unconventional roles of known drugs in cancer treatment."

Journal • Breast Cancer • CNS Disorders • Lung Cancer • Oncology • Psychiatry • Solid Tumor • AATF • DNMT3B

Patient Characteristics and Treatment Approaches in Delusional Infestation Across Two Medical Centers: A Retrospective Study. (PubMed, Skin (Milwood)) - "Treatments most often involved antiparasitic agents, pimozide, and second-generation antipsychotics; pimozide was associated with the highest rate of improvement...Despite varied diagnostic approaches, treatment outcomes remain poor. Multidisciplinary care and standardized protocols are needed to improve management and outcomes."

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

From Pimozide to Risperidone: Contemporary Antipsychotic Treatment of Delusional Parasitosis (APA 2026) - "Available evidence suggests that second-generation antipsychotics, particularly risperidone at low-to-moderate doses, are effective and generally well tolerated in the treatment of delusional parasitosis. Although the evidence base remains largely observational, these findings provide practical guidance for clinicians managing DP in dermatology, emergency, and consultation-liaison psychiatry settings."

CNS Disorders • Restless Legs Syndrome

Dual action of pimozide through lysosome disruption and inhibition of STATs induces apoptosis in chronic lymphocytic leukemia (CLL). (PubMed, Blood Adv) - "Pimozide also synergizes with venetoclax to induce apoptosis in CLL cells even following IL-4/CD40L signaling. This suggests that dual targeting of lysosomal function and STAT signaling represents a promising therapeutic approach to improve venetoclax efficacy and overcome TME-mediated drug resistance in CLL."

IO biomarker • Journal • Chronic Lymphocytic Leukemia • CNS Disorders • Hematological Malignancies • Leukemia • Oncology • CD40LG • IL4 • MCL1 • STAT5

A Cohort-Based Study of Patients With Delusional Infestation: Characterizing the Patient Population. (PubMed, J Cutan Med Surg) - "We report a 2-fold increase in the incidence of DI and significant female predominance in our study population. The majority of patients experience symptoms of living infestation, with non-specific "bugs" or "parasites" being the most common delusion."

Journal • CNS Disorders • Depression • Dermatology • Mental Retardation • Mood Disorders • Psychiatry

Integrative systems biology and drug repurposing reveal key regulatory hubs and a prognostic signature in gastric cancer. (PubMed, Discov Oncol) - "This comprehensive pipeline identified key molecular drivers, upstream regulators, survival-associated biomarkers, and potential therapeutic compounds in gastric cancer. The findings offer a robust framework for future experimental validation and contribute to the development of personalized therapeutic strategies for improving clinical outcomes in gastric cancer."

Journal • Gastric Cancer • Oncology • Solid Tumor • CDC37 • CTNNB1 • HSP90AB1 • SRSF7

NL6220204217: HAMLETT. Handling Antipsychotic Medication: Long-term Evaluation of Targeted Treatment. A study comparing continuation versus discontinuation/dose reduction of antipsychotic medication in patients remitted after a first episode of psychosis (clinicaltrialsregister.eu) - P4 | N=444 | Active, not recruiting | Sponsor: Universitair Medisch Centrum Groningen | Not yet recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Psychiatry

Targeting STAT5A via CRISPR/Cas9 restores TKI sensitivity in resistant chronic myeloid leukemia cells. (PubMed, Med Oncol) - "These findings identify STAT5A as a mechanistically validated and clinically actionable target, supporting its potential for combination strategies with TKIs or STAT5 inhibitors such as pimozide...STAT5A emerges as a compelling therapeutic target, meriting further investigation in preclinical models and patient-derived samples to evaluate its translational potential. Future validation in patient-derived CD34⁺ CML models may advance STAT5A-based therapeutic design."

Journal • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • ANXA5 • BCL2L1 • CASP3 • CASP8 • CCND1 • CD34 • CDKN2B • JAK2 • STAT5 • STAT5AWqe

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

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

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