perphenazine / Generic mfg. - LARVOL DELTA

Digging deep to uncover rare CYP genotypeSolanidine analysis during TDM revealed rare CYP2D6 poor metabolizer genotype: a case report (WFSBP 2026) - "The patient had a history of side effects during use of the CYP2D6 substrates perphenazine and aripiprazole at standard doses. This report shows the clinical value and feasibility of routine analysis of solanidine and 4-hydroxysolanidine to identify patients predicted to be CYP2D6 PMs, including patients with rare variants. • Solanidine measurements can be used as a complementary tool to genotyping • Phenotyping can substantially reduce the number-needed-togenotype for identification of CYP2D6 PMs in clinical practice."

Case report • Clinical • CNS Disorders

Bio-derived cellulose adsorbent from licorice residues for high-efficiency and recyclable removal of phenothiazines. (PubMed, Int J Biol Macromol) - "Removal kinetics reached equilibrium after 20 min and the adsorption capacities for chlorpromazine and perphenazine were 9.17 and 26.87 mg/g, respectively. As such, the plant-derived adsorbent eliminates the risk of causing secondary environmental pollution. This study established a practical and sustainable strategy to the issues of high-value utilization of herbal residues and remediation of pharmaceutical pollutants."

Journal

Evaluation of D3 Receptor Occupancy Using FLUORTRIOPRIDE ([18F]FTP) PET/CT (clinicaltrials.gov) - P1/2 | N=30 | Active, not recruiting | Sponsor: University of Pennsylvania | Trial completion date: Jun 2026 ➔ Jun 2027 | Trial primary completion date: Jun 2026 ➔ Jun 2027

Trial completion date • Trial primary completion date

Targeting CDK4 with repurposing perphenazine inhibited the growth of gastric cancer AGS and HGC27 cells by arresting cell cycle. (PubMed, Biochem Pharmacol) - "Palbociclib significantly enhanced this effect, while INK4C-IN-2 significantly reversed this blocking effect. In summary, we found a novel anti-tumor indication of antipsychotic drug perphenazine, which can inhibit the growth of tumor in vitro and in mouse-derived tumor model. These results suggested that perphenazine is also a promising anti-gastric cancer drug in clinical applications."

Journal • CNS Disorders • Gastric Cancer • Metabolic Disorders • Oncology • Solid Tumor • CDK4 • CDKN2C

Integrative In Silico Identification of TP53-Associated Drug Repurposing Candidates in Lung Adenocarcinoma. (PubMed, Pharmaceuticals (Basel)) - "Additionally, LUAD cell lines displayed consistent sensitivity signals for dropropizine (p = 8.47 × 10-3), terazosin (p = 1.11 × 10-3), morantel (p = 9.05 × 10-3), netilmicin (p = 8.37 × 10-3), altretamine (p = 9.82 × 10-3), and perphenazine (p = 9.58 × 10-3). Based on TP53-associated drug sensitivity profiles, this in silico analysis identifies atropine among the prioritized candidates, showing the strongest TP53-associated sensitivity signal in LUAD cell lines. Although experimental validation is required, the integration of independent computational datasets provides a robust framework for candidate prioritization and our findings provide a rationale for further preclinical investigation of atropine and related compounds in LUAD."

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • TP53

Priapism Associated with Psychiatric Medications: Clinical Case and Literature Review (APA 2026) - "History includes priapism with Perphenazine, Quetiapine, and Haloperidol, and other unknown antipsychotics...Other psychiatric medications that reported at least greater incidences of priapism include Quetiapine, Risperidone, Aripiprazole, Sertraline, Methylphenidate, and Clozapine...Agents like trazodone and olanzapine carry the highest risk, independent of dose, with risk heightened by drug interactions or rapid titration...Timely recognition and adverse event reporting can also contribute to improved pharmacovigilance and patient safety. [4,5]"

Clinical • Review • CNS Disorders • Erectile Dysfunction • Psychiatry • Schizophrenia • ADRA1B

Learning Outcomes That Maximally Differentiate Psychiatric Treatments. (PubMed, Int J Methods Psychiatr Res) - P4 | "SV enables precision psychiatry by optimizing outcome definitions to enhance treatment differentiation in RCTs. This approach provides interpretable, clinically actionable insights using existing trial data, without requiring complex predictive modeling or additional biomarkers."

Clinical • Journal • CNS Disorders • Depression • Psychiatry • Schizophrenia

Stereoselective cyclic peptide assisted DART-MS for rapidly screening environmental disruptors of dopamine receptors. (PubMed, Talanta) - "Only the CPP-sulpiride and CPP-pramipexole complexes showed stability reduction by 85% and 61% in DART-MS compared to ESI-MS. Although the spiked model ligand perphenazine (L1) was not captured by the CPP, the rubber additive 1,3-diphenylguanidine was successfully identified, a DA antagonist formerly also discovered by the ESI-MS-based BDA workflow. Collectively, this study establishes DART-MS-based BDA as a highly-efficient screening tool for future large-scale surveillance of GPCR-disrupting chemicals in the environment."

Journal • CNS Disorders • Psychiatry

First-generation antipsychotic shortages in the United States: Utilization and switching patterns. (PubMed, Explor Res Clin Soc Pharm) - "Most were receiving haloperidol (n = 52,344, 54.5%) and perphenazine (n = 16,966, 17.7%). Switching was common among individuals receiving thiothixene (32.8%), trifluoperazine (55.2%), and molindone (100%). Time to first switch ranged from 22 (standard deviation [SD]: 21) to 103 (SD: 66) days. Shortages of FGAs may influence patients' switching to other agents, including second generation antipsychotics."

Journal • CNS Disorders

Clozapine After 1 Failed Antipsychotic Drug Trial in First-Episode Psychosis: A Randomized Clinical Trial. (PubMed, JAMA Psychiatry) - P3 | "In phase 1, patients with FEP were randomized to receive oral olanzapine, risperidone, amisulpride, aripiprazole, or perphenazine for 8 weeks. This study provides some evidence for clinicians to consider regarding use of clozapine as the next sequential treatment after patients have failed an adequate trial with 1 of the more traditional antipsychotics. ClinicalTrials.gov Identifier: NCT03510325."

Clinical • Journal • CNS Disorders • Psychiatry • Schizophrenia • Schizophreniform Disorder

Early AI-driven repurposing study of existing drugs towards the vasopressin V2 receptor. (PubMed, Comput Biol Med) - "Five drugs were shortlisted as promising candidates for V2R: cabergoline, clopidogrel, cloxacillin, perphenazine, and zafirlukast...Interestingly, zafirlukast, at single-digit nanomolar concentration significantly reduced the DDAVP-dependent cAMP production and water reabsorption, with effects comparable to tolvaptan, a well-known selective V2R antagonist...Induced-fit docking simulations demonstrated that zafirlukast engages V2R by adopting a binding conformation closely resembling that of X-ray solved vasopressin. Taken together, our results support the repurposing of zafirlukast as a promising V2R antagonist candidate."

Journal • Oncology • CD4

Phenothiazines enhance antibacterial activity of macrophage by inducing ROS and autophagy. (PubMed, Front Immunol) - "Furthermore, perphenazine (PHZ) effectively reduced organ lesions and inflammation associated with S. Typhimurium infections in vivo. Our results demonstrated that phenothiazines are lead compounds for antibacterial agents via HDTs."

Journal • Infectious Disease • Inflammation

Nationwide health claims analysis of phenothiazine-associated retinopathy risk in chlorpromazine and perphenazine users. (PubMed, Sci Rep) - "In multivariable models, perphenazine use (vs. chlorpromazine), older age, female sex, diabetes, hypertension, and hyperlipidemia were all significant predictors of the outcomes (all P < 0.05). These findings demonstrate that both drugs carry a modest risk of retinal toxicity-particularly perphenazine-and support the need for proactive ophthalmic screening in this population."

HEOR • Journal • Retrospective data • Cardiovascular • Diabetes • Dyslipidemia • Hypertension • Inherited Retinal Dystrophy • Macular Degeneration • Metabolic Disorders • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

Recommendations of Enhanced Recovery Interventions for Patient's Clinical Team and Collection of Associated Data (clinicaltrials.gov) - P3 | N=2977 | Completed | Sponsor: Jennifer Holder-Murray | Recruiting ➔ Completed | Trial completion date: Dec 2025 ➔ Mar 2025 | Trial primary completion date: Dec 2025 ➔ Mar 2025

Trial completion • Trial completion date • Trial primary completion date

Efficacy and Tolerability of Seven Antipsychotic Drugs in Acutely Ill Patients With Schizophrenia: A Randomized, Multicenter, Assessor-Blinded Trial. (PubMed, Am J Psychiatry) - "Eligible inpatients 18-45 years of age with schizophrenia experiencing acute exacerbation were recruited and randomized to 6 weeks of monotherapy with one of seven antipsychotic drugs: olanzapine, risperidone, quetiapine, aripiprazole, ziprasidone, perphenazine, and haloperidol. This trial fills important knowledge gaps in acute antipsychotic treatment of schizophrenia. It confirms hierarchies in efficacy and side effects of antipsychotics from related evidence."

Journal • CNS Disorders • Psychiatry • Schizophrenia

Psychotropic and neurodegenerative drugs modulate platelet activity via the PAF pathway. (PubMed, Neurochem Int) - "Results revealed that most of the compounds assessed inhibited more effectively the PAF-induced aggregation of platelets compared to their effect on the ADP-pathway, with perphenazine showing the greatest anti-PAF potency. Several drug combinations, notably those including alprazolam and diclofenac, demonstrated significant synergistic effects. These findings suggest that commonly prescribed psychotropic drugs and medications for neurodegenerative disorders can influence platelet activity, mostly through the PAF-pathway, and that their interactions with NSAIDs may amplify their efficacy. Nevertheless, some drugs and their combinations induced lysis of platelets at much higher concentrations than their IC50 values, which stems safety concerns for their use."

Journal • Alzheimer's Disease • CNS Disorders • Depression • Mood Disorders • Movement Disorders • Parkinson's Disease • Psychiatry • Schizophrenia

Clinical effectiveness and safety in psychosis with comorbid pulmonary thromboembolism treated with long-acting injectable Aripiprazole every two months (ECNP 2025) - "A recent meta-analysis concluded that both first- and second-generation antipsychotics significantly increase the risk of VTE and pulmonary embolism (PE), with olanzapine, clozapine, haloperidol, perphenazine, and risperidone showing the highest association [1]...The patient also accepted anticoagulant therapy with dabigatran 150 mg...Conclusions Antipsychotics, particularly olanzapine, may raise the risk of serious thromboembolic events even in young patients without clear risk factors. Aripiprazole, both oral and LAI, is a safe, effective alternative in patients with VTE history, enabling ongoing antipsychotic treatment without compromising vascular safety."

Clinical • CNS Disorders • Psychiatry • Schizophrenia

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

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

Evaluation of D3 Receptor Occupancy Using FLUORTRIOPRIDE ([18F]FTP) PET/CT (clinicaltrials.gov) - P1/2 | N=30 | Active, not recruiting | Sponsor: University of Pennsylvania | Trial completion date: Jun 2025 ➔ Jun 2026 | Trial primary completion date: Jun 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date

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

Solanidine analysis during therapeutic drug monitoring revealed rare CYP2D6 poor metabolizer genotype: A case report. (PubMed, Br J Clin Pharmacol) - "The patient had a history of side effects during use of the CYP2D6 substrates perphenazine and aripiprazole at standard doses. The report shows the clinical value and feasibility of analysing solanidine and 4-hydroxysolanidine as part of routine therapeutic drug monitoring to identify patients predicted to be CYP2D6 PMs and who should be selected for genotyping, including patients with rare variants not included in standard genotyping panels. Solanidine and 4-hydroxysolanidine semiquantitation can be used as a complementary tool to genotyping and substantially reduce the number-needed-to-genotype for identification of CYP2D6 PMs in clinical practice."

Journal

Toward pharmacologic therapy for glioblastoma: Identifying inhibitors of very long-chain acyl-CoA synthetase 3 (ACSVL3). (PubMed, bioRxiv) - "These included drugs triflupromazine, phenazopyridine, chlorpromazine, emodin, and perphenazine which are approved for treating other conditions. Although secondary screening will likely exclude many or all of these, our findings support the notion that we have developed a viable method for detecting potential ACSVL3 inhibitors. Further characterization may reveal candidate pharmacologic agents for treatment of GBM and other cancers."

Journal • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor • ACSL3 • SLC27A2

In-vivo Pharmacokinetic Assessment and In-vitro Characterization of Strategically Optimized Perphenazine-loaded Nanostructured Lipid Carriers for Nose-to-brain Targeting. (PubMed, Recent Pat Nanotechnol) - "These results suggested the superiority of NLCs in enhancing the bioavailability of PPZ drug and their suitability for successful brain targeting, which could be subject to a patent application to protect the novel formulation."

Journal • PK/PD data • Preclinical • CNS Disorders • Psychiatry • Schizophrenia

Recommendations of Enhanced Recovery Interventions for Patient's Clinical Team and Collection of Associated Data (clinicaltrials.gov) - P3 | N=2500 | Recruiting | Sponsor: Jennifer Holder-Murray | Trial completion date: Jun 2025 ➔ Dec 2025 | Trial primary completion date: Jun 2025 ➔ Dec 2025

Trial completion date • Trial primary completion date