Serlect (sertindole) / Lundbeck, Abbott - LARVOL DELTA

Mining and analysis of drug-induced shock adverse reactions: A comprehensive pharmacovigilance study based on the US FAERS database. (PubMed, PLoS One) - "This study demonstrates strong associations between specific drug classes and shock, with cardiovascular, anti-infective, and nervous system agents identified as the most critical categories. The application of advanced multi-method signal detection enhances the accuracy of pharmacovigilance, reveals novel associations, and provides important evidence for clinical monitoring and risk management."

Adverse events • Journal • Retrospective data • Cardiovascular

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

Automated phenotypic analysis and classification of drug-treated cardiomyocytes via synergized time-lapse holographic imaging and deep learning. (PubMed, Comput Methods Programs Biomed) - "Our implementation allowed precise single drug-treated CM motion tracking and in-depth investigation and automated classification of CMs via synergized time-lapse holographic imaging and deep learning."

Journal • Cardiovascular

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

Antipsychotic drug dosing and study discontinuation in schizophrenia: A systematic review and dose-response meta-analysis. (PubMed, Eur Neuropsychopharmacol) - "Dose discontinuation curves varied between the antipsychotics and included U-shaped, monotonic, and hyperbolic patterns. Future studies should consistently present disease-related and side-effect-related dropouts due to adverse events separately."

Journal • Retrospective data • Review • CNS Disorders • Psychiatry • Schizophrenia

Molecular Modeling of Vasodilatory Activity: Unveiling Novel Candidates Through Density Functional Theory, QSAR, and Molecular Dynamics. (PubMed, Int J Mol Sci) - "According to the binding energies results, this study identifies novel vasodilatory candidates where Dasabuvir and Sertindole seem to have potent and selective activity, offering promising avenues for the development of next-generation cardiovascular therapies. Finally, this research bridges computational modelling with experimental validation, providing valuable insight for the design of optimized vasodilatory agents to address critical unmet needs in cardiovascular medicine."

Journal • Cardiovascular

Repurposed drugs as histone deacetylase 8 inhibitors: Implications in cancer and neuropathological conditions. (PubMed, Front Pharmacol) - "Principal component analysis and Gibbs free energy calculations strongly recommend that both complexes were highly stable during the simulation. Overall, the results indicate that radotinib and sertindole can be promising candidates as HDAC8-targeting repurposed drugs against cancer and neuropathological conditions."

Epigenetic controller • Journal • CNS Disorders • Oncology • HDAC8

Understanding the interactions between repurposed drugs sertindole and temoporfin with receptor for advanced glycation endproducts: Therapeutic implications in cancer and metabolic diseases. (PubMed, J Mol Model) - "To gain deeper insights into the binding mechanisms of the elucidated candidate repurposed drugs, sertindole and temoporfin with RAGE, we conducted extensive all-atom MD simulations, spanning 500 nanoseconds (ns). These simulations elucidated the conformational dynamics and stability of the RAGE-sertindole and RAGE-temoporfin complexes."

Journal • Metastases • CNS Disorders • Metabolic Disorders • Oncology

Trajectories of Daily Antipsychotic Use and Weight Gain/Metabolic Changes in People Hospitalized for First Episode of Psychosis (SIRS 2024) - "Greater antipsychotic exposure was associated with greater BMI increase, but only in people with normal/low baseline BMI, who were treated with clozapine, olanzapine, sertindole, or quetiapine. Conclusions Clinicians should be especially cautious in prescribing metabolically more problematic antipsychotics to people with a normal to low baseline BMI. Weight was the best predictor of metabolic alterations, thus emphasizing regular weight monitoring during antipsychotic treatment."

Clinical • CNS Disorders • Schizophrenia

Paliperidone LAI-Induced Leukocytopenia: A Case Report (EPA 2024) - "She is currently stable taking sertindole 16 mg/day, clonazepam 2 mg/day and alprazolam 0.5 mg/day...It has been proposed that drug-induced neutropenia is often dose-dependent, which could explain why our patient exhibited tolerability to risperidone but developed cytopenia upon transitioning to depot paliperidone. While cases of agranulocytosis have been reported in association with the use of other antipsychotics these antipsychotics do not require the same monitoring as clozapine. Our case emphasizes the need for vigilant blood dyscrasia monitoring during antipsychotic therapy."

Clinical • CNS Disorders • Psychiatry • Schizophrenia

Molecular docking as a tool for the discovery of novel insight about the role of acid sphingomyelinase inhibitors in SARS- CoV-2 infectivity. (PubMed, BMC Public Health) - "Also, we outlined ASMase structure and underlying mechanisms inhibiting viral entry 40 with the aid of inhibitors of acid sphingomyelinase (FIASMAs). In silico molecular docking analyses of FIASMAs with inhibitors revealed that dilazep (S = - 12.58 kcal/mol), emetine (S = - 11.65 kcal/mol), pimozide (S = - 11.29 kcal/mol), carvedilol (S = - 11.28 kcal/mol), mebeverine (S = - 11.14 kcal/mol), cepharanthine (S = - 11.06 kcal/mol), hydroxyzin (S = - 10.96 kcal/mol), astemizole (S = - 10.81 kcal/mol), sertindole (S = - 10.55 kcal/mol), and bepridil (S = - 10.47 kcal/mol) have higher inhibition activity than the candidate drug amiodarone (S = - 10.43 kcal/mol), making them better options for inhibition."

Journal • Review • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

The cellular mechanism of antipsychotic-induced myocarditis: A systematic review. (PubMed, Schizophr Res) - "Antipsychotics examined in the included studies included clozapine (n = 13), ziprasidone (n = 1), amisulpride (n = 1), haloperidol (n = 1), levomepromazine (n = 1), olanzapine (n = 1), and sertindole (n = 1). Discovery of the mechanism by which antipsychotic drugs induce myocarditis will allow the development of clinically-useful biomarkers to identify those patients at increased risk prior to drug exposure. The development or repurposing of therapeutics to prevent or treat drug-induced myocarditis will also be possible and this will enable increased and safe use of antipsychotics for those patients in need."

Journal • Review • Cardiovascular • CNS Disorders • Inflammation

Computational prognostic evaluation of Alzheimer's drugs from FDA-approved database through structural conformational dynamics and drug repositioning approaches. (PubMed, Sci Rep) - "Donepezil and galantamine were implanted as standard drugs and drugs were screened out based on structural similarities. Finally, MD simulation study were carried out on these drugs and evaluated their stability behavior by generating root mean square deviation and fluctuations (RMSD/F), radius of gyration (Rg) and soluble accessible surface area (SASA) graphs. Taken together, darifenacin, astemizole, tubocurarine, elacridar, sertindole and tariquidar displayed good lead like profile as compared with standard and can be used as possible therapeutic agent in the treatment of AD after in-vitro and in-vivo assessment."

FDA event • Journal • Alzheimer's Disease • CNS Disorders

Inhibition of voltage-dependent K channels in rabbit coronary arterial smooth muscle cells by the atypical antipsychotic agent sertindole. (PubMed, J Appl Toxicol) - "These findings demonstrate the sertindole dose-dependent and use-independent inhibition of vascular Kv channels (mainly the Kv1.5 subtype) through a mechanism that involves altering steady-state inactivation curves. Therefore, the use of sertindole as an antipsychotic drug may have adverse effects on the cardiovascular system."

Journal • Preclinical • Cardiovascular • CNS Disorders

A network meta-analysis of efficacy, acceptability, and tolerability of antipsychotics in treatment-resistant schizophrenia. (PubMed, Eur Arch Psychiatry Clin Neurosci) - "Clozapine remains the gold standard for patients with treatment-resistant schizophrenia. Olanzapine seems to be second-best and could be tried before switching to clozapine."

Journal • Retrospective data • Anesthesia • CNS Disorders • Psychiatry • Schizophrenia

Antipsychotic dose, dopamine D2 receptor occupancy and extrapyramidal side-effects: a systematic review and dose-response meta-analysis. (PubMed, Mol Psychiatry) - "Almost all antipsychotics were associated with dose-dependent EPS with varied degrees and the maximum ORs ranged from OR = 1.57 95%CI [0.97, 2.56] for aripiprazole to OR = 7.56 95%CI [3.16, 18.08] for haloperidol at 30 mg/d...There was very low quality of findings for cariprazine, iloperidone, and zotepine, and no data for clozapine...In conclusion, we found that the risk of EPS increases with rising doses and differs substantially in magnitude among antipsychotics, yet exceptions were quetiapine and sertindole with negligible risks. Our data provided additional insights into the current DR therapeutic window for EPS."

Adverse events • Retrospective data • Review • CNS Disorders • Movement Disorders • Parkinson's Disease • Psychiatry • Schizophrenia • DRD2

Sertindole, an Antipsychotic Drug, Curbs the STAT3/BCL-xL Axis to Elicit Human Bladder Cancer Cell Apoptosis In Vitro. (PubMed, Int J Mol Sci) - "Overall, the current study indicated sertindole exerts bladder cancer cytotoxicity by provoking apoptosis through targeted inhibition of the antiapoptotic STAT3/BCL-xL signaling axis. These findings implicate the potential to repurpose sertindole as a therapeutic strategy for bladder cancer."

Journal • Preclinical • Bladder Cancer • CNS Disorders • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Oncology • Psychiatry • Schizophrenia • Solid Tumor • Urothelial Cancer • BCL2L1 • STAT3

Human Hemoglobin and Antipsychotics Clozapine, Ziprasidone and Sertindole: Friends or Foes? (PubMed, Int J Mol Sci) - "On the other hand, bound ziprasidone and sertindole had a slightly pro-oxidative effect, increasing ferrihemoglobin content, a possible "foe". Since the interaction of proteins with drugs plays a vital role in their pharmacokinetic and pharmacodynamic properties, the physiological significance of the obtained findings is briefly discussed."

Journal • CNS Disorders

Antipsychotic-induced akathisia in adults with acute schizophrenia: A systematic review and dose-response meta-analysis. (PubMed, Eur Neuropsychopharmacol) - "We obtained data on all antipsychotics except clozapine and zotepine. In patients with acute exacerbations of chronic schizophrenia, from moderate to high certainty of evidence, our analysis showed that sertindole and quetiapine carried negligible risks for akathisia across examined doses (flat curves), while most of the other antipsychotics had their risks increase initially with increasing doses and then either plateaued (hyperbolic curves) or continued to rise (monotonic curves), with maximum ORs ranging from 1.76 with 95% Confidence Intervals [1.24, 2.52] for risperidone at 5.4 mg/day to OR 11.92 [5.18, 27.43] for lurasidone at 240 mg/day...In conclusion, liability of akathisia varies between antipsychotics and is dose-related. The dose-response curves for akathisia in most antipsychotics are either monotonic or hyperbolic, indicating that higher doses carry a greater or equal risk compared to lower doses."

Journal • Retrospective data • Review • CNS Disorders • Movement Disorders • Psychiatry • Schizophrenia

Longitudinal Investigation of Metabolic Changes, Weight Gain, and Medication Exposure in First Episode Psychosis (SOBP 2023) - "For participants with FEP, we collected cumulative and average daily antipsychotic exposure between visits, which we further categorized into metabolically problematic (clozapine, olanzapine, sertindole and quetiapine) or not. Conclusions Participants with FEP showed BMI increase in a short period that was associated with exposure to specific medications, and metabolic changes consistent with metabolic syndrome. Greater care should be taken when prescribing metabolically problematic antipsychotics for people with lower BMI."

CNS Disorders • Psychiatry • Schizophrenia

The risk of developing diabetes during antipsychotic drug treatment: A nationwide study among 31,856 patients with schizophrenia (EPA 2023) - "This risk was particularly increased among individuals treated with lurasidone (HRR: 2.66, 95%CI: 1.10-6.42), sertindole (HRR: 2.10, 95%CI 1.51-2.93), paliperidone (HRR: 1.84, 95%CI 1.47-2.31), clozapine (HRR: 1.74, 95%CI 1.49-2.03) and aripiprazole (HRR: 1.54, 95%CI 1.35-1.75), whereas treatment with zuclopenthixol (HRR: 1.00, 95%CI 0.82-1.23), flupentixol (HRR: 0.71, 95%CI 0.40-1.25) and pimozide (HRR: 0.74, 95%CI 0.31-1.78) were not associated with an increased risk of diabetes. This real-world study indicates differences in the risk of developing diabetes between specific AP compounds. Further analyses will be presented at the conference."

Clinical • CNS Disorders • Psychiatry • Schizophrenia

Antibacterial and Antibiofilm Activities of Sertindole and Its Antibacterial Mechanism against Staphylococcus aureus. (PubMed, ACS Omega) - "The two-component system VraS/VraR knockout S. epidermis strain also showed enhanced sensitivity to sertindole. Overall, our data suggested that sertindole exhibited antibacterial and biofilm-inhibiting activities against S. aureus and that its antibacterial actions may involve the destruction of cell integrity."

Journal • Infectious Disease

Antipsychotics and risk of QT prolongation: a pharmacovigilance study. (PubMed, Psychopharmacology (Berl)) - "This large study in a real-world setting suggests that sertindole and ziprasidone were the antipsychotics drugs associated with the highest risk of QT prolongation reporting. Our results suggest that lurasidone is less associated with QT interval prolongation reports. Our study also suggests that antipsychotics with the higher hERG affinity are more associated with to QT prolongations reports."

Adverse events • Journal • CNS Disorders

Antipsychotic Drug-Mediated Adverse Effects on Rat Testicles May Be Caused by Altered Redox and Hormonal Homeostasis. (PubMed, Int J Mol Sci) - "A study was undertaken to investigate whether 28-day long treatment with clozapine, ziprasidone or sertindole (using a recommended daily dose for atypical antipsychotic therapy), induced histopathological changes both in rat testicles and prostate, changed the activity of the antioxidant defence system and altered blood testosterone and prolactin. Our results demonstrate that APDs have the capacity to change both redox and endocrinological balance. One or both outcomes could underline testicular degeneration and disturbed spermatogenesis."

Adverse events • Journal • Preclinical • CNS Disorders • Psychiatry • Schizophrenia • Sexual Disorders

Role of the NRG1/ErbB4 and PI3K/AKT/mTOR signaling pathways in the anti-psychotic effects of aripiprazole and sertindole in ketamine-induced schizophrenia-like behaviors in rats. (PubMed, Inflammopharmacology) - "The proposed pathway was investigated by injecting LY294002 (a selective PI3K inhibitor) (25 μg/kg, intrahippocampal injection) 30 min before the drugs. This study reveals that the antipsychotic effects of aripiprazole and sertindole are partly due to oxidative stress reduction as well as NRG1/ErbB4 and PI3K/AKT/mTOR signaling pathways activation. The NRG1/ErbB4 and PI3K signaling pathways may offer a new therapeutic approach for treating schizophrenia in humans."

Journal • Preclinical • CNS Disorders • Mental Retardation • Psychiatry • Schizophrenia • ERBB4 • NRG1