thioridazine / Generic mfg. - LARVOL DELTA

Capsular polysaccharide can sensitize bacteria to non-antibiotic drugs. (PubMed, bioRxiv) - "Here, we show that the K5 CPS of Escherichia coli Nissle 1917 ( EcN ) sensitizes it to thioridazine (TDZ) and related antipsychotics...These findings demonstrate that canonically protective surface structures can become vulnerabilities under non-antibiotic pharmaceutical pressure. Human medications may therefore inadvertently shape the expression and evolution of bacterial surface structures in the gastrointestinal tract, challenging presumptions of CPS-mediated environmental protection."

Journal • CNS Disorders • Gastrointestinal Disorder

Assessment of psychotropic medicines utilization patterns for the treatment of mental and neurological disorders in Public Hospitals of Hadiya Zone, Southern Ethiopia: A record-based study. (PubMed, PLOS Ment Health) - "Chlorpromazine, haloperidol, and thioridazine were the top three most prescribed antipsychotics which constituted 71.34% of antipsychotics use in public hospitals of Hadiya zone...Among antidepressants, amitriptyline, a tricyclic antidepressant, was most frequently prescribed (74.9%), followed by fluoxetine, selective serotonin reuptake inhibitor (21.5%)...Chlorpromazine, Amitriptyline, and Risperidone showed a higher proportion of utilized medicines...Close to 10% of psychiatric patients had a treatment switch, mostly because of poor improvement, relapse, side effects, and non-adherence. Further prospective continuous studies on both prevalence and use patterns need to be undertaken to get more information."

Journal • CNS Disorders • Depression • Epilepsy • Mood Disorders • Psychiatry • Schizophrenia

Exosomal gene-based predictive model and therapeutic target identification for Alzheimer's disease: A bioinformatics analysis. (PubMed, PLoS One) - "Our comprehensive analyses successfully established a reliable exosomal gene-based model for predicting AD pathogenesis, and identified relevant pharmacological networks and core molecular docking targets, providing novel insights for AD diagnosis and targeted therapy."

Journal • Alzheimer's Disease • CNS Disorders • CXCR4 • TUBB

Rational Design, Synthesis, Molecular Docking, and Evaluation of Thioridazine-modified Tetrahydrocarbazole Derivatives as Antitubercular Agents. (PubMed, Recent Adv Antiinfect Drug Discov) - "Thioridazine-derived tetrahydrocarbazoles showed antitubercular activity against M. tuberculosis H37Rv with MIC values comparable to pyrazinamide. Further, the lead compounds demonstrated reduced BBB permeability and favourable selectivity towards M. tuberculosis over VERO cells. The docking study provided supportive, nonmechanistic insights into possible CmaA2 interaction. These findings warrant further in vivo evaluation and mechanistic investigation."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Gut-brain axis crosstalk in patients with Alzheimer's disease and high body mass index: Gut dysbiosis, blood-brain barrier disruption, and neuroinflammation. (PubMed, J Alzheimers Dis) - "In AD-hBMI group, elevated thioridazine, 4-hydroxybenzaldehyde, and N-acetylleucine were positively correlated with ZO-1 level in CSF, reduced acesulfame and undecanoic acid were negatively correlated with OCLN level in CSF, and elevated (S)-S-methylcysteine sulfoxide was positiveiy correlated with both ZO-1 and OCLN levels in CSF. Elevated thioridazine and medroxyprogesterone were positively correlated with NO level in CSF, and decreased butyric acid was negatively correlated with ·OH level in CSF.ConclusionsHigh BMI may accelerate gut dysbiosis, leading to disrupted BBB, enhanced neuroinflammation, and ultimately accelerated cognitive impairment in AD patients."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Inflammation • Solid Tumor • OCLN • TJP1

Synergistic Photothermal-Chemotherapy of Hepatocellular Carcinoma and Cancer Stem Cells via in situ pH-Responsive Hydrogels. (PubMed, Int J Nanomedicine) - "To further improve the therapeutic effect against tumors, in this study, the chemotherapeutic agent thioridazine (THZ) was loaded into a gel network formed by the Schiff base cross-linking of amino-functionalized graphene quantum dots (NH2-GQDs) and oxidized dextran...In vivo experiments demonstrated that NTD@Gel combined with near-infrared laser irradiation significantly inhibited tumor growth, reduced CD133 and CD326 expression on tumor cells, effectively prolonged the survival time of tumor-bearing mice, and caused no obvious pathological damage in the major organs of mice. NTD@Gel can significantly enhance the therapeutic efficacy against hepatocellular carcinoma and reduce the risk of metastasis and recurrence through the synergistic effect of photothermal therapy and chemotherapy."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor • CD133

Drugs that act on both G protein-coupled receptors (GPCRs) and kinases: potentiation of effects, side effects and general aspects of drug pleiotropy. (PubMed, Br J Pharmacol) - "Drug pleiotropy among GPCRs and kinases is a occurring phenomenon. Structural factors that may contribute to pleiotropy include chemical similarity to endogenous ligands, lipophilicity and planarity of chemical structure, which may guide the development of drugs with intentional multi-target effects. Although pleiotropy presents challenges in ensuring selectivity, it also creates opportunities for innovative therapeutic strategies if strategically applied."

Adverse events • Journal • Review

A model of polymicrobial catheter-associated urinary tract infection reveals biofilm-mediated modulation of treatment efficacy. (PubMed, J Appl Microbiol) - "We show that our system establishes stable and reproducible polymicrobial communities and facilitates analysis across both planktonic and biofilm lifestyles. We confirm that polymicrobial biofilms in this system display distinct population dynamics compared to planktonic populations and modulate the impact of ciprofloxacin treatment by protecting the most susceptible community members. In addition, we demonstrate the capacity of P. mirabilis to encrust and block catheters when part of a polymicrobial community and confirm that thioridazine treatment remains effective at inhibiting catheter blockage under these conditions."

Journal • Infectious Disease • Nephrology • Pneumonia

Fatty acid oxidation drives acetyl-CoA-dependent H3K9ac reprogramming to promote adaptive resistance to BRAFV600E inhibition in thyroid cancer. (PubMed, Cell Death Dis) - "Through integrated transcriptomic and metabolomic analyses, we demonstrate that BRAFi by vemurafenib (PLX4032) significantly enhances FAO in thyroid cancer cells. The pharmacological inhibition of FAO via thioridazine (Thio) synergizes with BRAFi to suppress tumor growth in vitro, in vivo and in a patient-derived organoid...Consistently, functional studies confirm RUNX1's oncogenic role, as its knockdown reduces cell proliferation, migration, and invasion. In conclusion, our work reveals a metabolic-epigenetic axis underlying adaptive response to BRAFi and identifies RUNX1 as a novel oncogene in thyroid cancer."

Journal • Oncology • Solid Tumor • Thyroid Gland Carcinoma • RUNX1

Overcoming Multidrug Resistance by Bacterial Efflux Pump Inhibitors in Clinical Escherichia coli Strains. (PubMed, Antibiotics (Basel)) - "This study examined efflux-mediated resistance in extended-spectrum beta-lactamase (ESBL)-producing E. coli and evaluated the potential of several efflux pump inhibitors (EPIs)-promethazine (PMZ), thioridazine (TZ), carbonyl cyanide m-chlorophenyl hydrazine (CCCP), reserpine (RES), and phenyl-arginine-β-naphthylamide (PAβN)-as therapeutic adjuncts...We observed a quite weak synergism between ciprofloxacin, ceftriaxone, and PMZ; however, the result was not significant. Overall, the results highlight the central role of efflux pumps in ESBL-producing E. coli and indicate that EPIs can reverse resistance (e.g., PMZ) and exhibit potent anti-biofilm activity and show additive interactions with antibiotics. However, further studies are needed to optimize their safety, pharmacokinetics, and antibiotic pairing for potential clinical use."

Journal

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

Role of efflux pump inhibitors in enhancing the effect of bedaquiline on M. tuberculosis. (PubMed, Future Microbiol) - "This study investigated the effects of classical efflux pump inhibitors (EPIs) thioridazine (THZ), chlorpromazine (CPZ), verapamil (VP), and reserpine (RSP) on bedaquiline (BDQ) susceptibility in Mycobacterium tuberculosis clinical isolates explored potential interactions of these compounds with the MmpL5-MmpS5 efflux system. EPIs substantially enhanced BDQ susceptibility in vitro, suggesting that efflux-mediated modulation of BDQ activity occurs. These findings provide comparative, exploratory evidence supporting EPIs as potential adjuvants and offer a reproducible experimental basis for selecting candidates for future translational and in vivo validation studies."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

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

Simultaneous Determination of Thioridazine and Its Metabolites by UHPLC-MS/MS With Application to a Pharmacokinetic Study in Rats. (PubMed, Biomed Chromatogr) - "All analytes were stable under the conditions used in this study. This method was applied in a pharmacokinetic study following the intravenous administration of thioridazine to rats."

Journal • PK/PD data • Preclinical

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

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

Repurposed Drugs and Efflux Pump Inhibitors Against Gram-Negative Urinary Tract Pathogenic Bacteria. (PubMed, Antibiotics (Basel)) - "Minimum inhibitory concentrations (MICs) of thioridazine (TZ), promethazine (PMZ), fluoxetine (Fx), sertraline (Sr), phenylalanine arginine β-naphthylamide (PAβN), carbonyl cyanide m-chlorophenyl hydrazone (CCCP), and the glutamine uptake inhibitor V9302 were determined at pH 5-8... TZ reduced biofilm formation in sensitive K. pneumoniae at all pH levels and enhanced ciprofloxacin (CIP) activity, whereas PMZ showed a weaker effect, limited mainly to neutral pH...V9302 was a potent biofilm inhibitor in K. pneumoniae and resistant E. coli and interfered with efflux activity, showing strong effects in acidic environments. Repurposed drugs and EPIs may be useful as antibiotic adjuvants or biofilm inhibitors in treating resistant UTIs."

Journal • Infectious Disease • Nephrology • Pneumonia

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

Identification and Characterization of Static Craniofacial Defects in Pre-Metamorphic Xenopus laevis Tadpoles. (PubMed, J Dev Biol) - "This study explores the differential remodeling responses of craniofacial defects by comparing the effects of two pharmacological agents, thioridazine-hydrochloride (thio) and ivermectin (IVM), on craniofacial morphology in X. laevis...Additionally, unique neuronal profiles suggest a previously underappreciated role for the nervous system in tissue remodeling. This study provides novel insights into the molecular and cellular mechanisms underlying craniofacial defect remodeling and lays the groundwork for future investigations into tissue repair in vertebrates."

Journal

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

Thioridazine induces phospholipid accumulation and necroptosis in parental and tamoxifen-resistant breast cancer cells. (PubMed, Mol Omics) - "Furthermore, thioridazine co-treatment enhances the efficacy of tamoxifen in resistant breast cancer cells, augmenting its potential for combinatorial treatment. Altogether, Thioridazine induces phospholipid accumulation followed by necroptosis in both parental and tamoxifen-resistant breast cancer cell lines, highlighting its potential application in breast cancer treatment."

Journal • Breast Cancer • CNS Disorders • Oncology • Solid Tumor • CDKN1A

Synergistic anticancer and antibacterial effects of novel regimens of phytopolyphenols and repurposing drugs on cultured cells. (PubMed, Oncol Res) - "This study evaluated the anticancer and antibacterial efficacy of PTM regimens that included phytopolyphenols (specifically curcumin (C) and green tea polyphenols (G)), repurposed drugs (memantine (Mem), thioridazine (TRZ), cisplatin (Cis), and 5-fluorouracil (5FU)), and ZnSO4 (Zn) across three cultured cancer cell lines and four cultured pathogens. Given that all drugs incorporated in the PTM regimens have been clinically validated for safety and efficacy, particularly regarding their synergistic selective anticancer efficacy, inhibition of efflux pump ATPase, and antibiofilm formation of pathogens, these regimens may offer a promising therapeutic strategy to alleviate the severe side effects and drug resistance typically associated with chemotherapeutic agents. Further preclinical and clinical investigations are warranted."

Journal • Infectious Disease • Oncology

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

A thioridazine-derived molecule exhibits potential anti-inflammatory activity through IKK inhibition. (PubMed, Inflammopharmacology) - "This study highlights the potential of ligand-based lead optimisation techniques for mitigating off-target effects, thereby offering a safer anti-inflammatory therapeutic candidate. By overcoming the cardiotoxicity associated with thioridazine, TDZ-D2 presents a promising avenue for drug development for inflammatory diseases."

Journal • Cardiovascular • Inflammation • NFKBIA