A. N. Pharmacia Laboratories · CHRM1 · 小分子
trifluoperazine + trihexyphenidyl 是一种小分子，由A. N. Pharmacia Laboratories研发。该药已获批，用于治疗相关适应症，给药途径：Oral (PO)。
| 商品名 | Fluhex forte, Fluhex, Fluhexette |
| 公司 | A. N. Pharmacia Laboratories |
| 药物类别 | 小分子 |
| 分子靶点 | CHRM1 |
| 给药途径 | Oral (PO) |
| 状态 | Approved |
trifluoperazine + trihexyphenidyl 作用于 1 个分子靶点：
| CHRM1 | cholinergic receptor muscarinic 1 (M1, HM1) |
trifluoperazine + trihexyphenidyl 针对 1 个适应症，涉及 1 个治疗领域。
| 治疗领域 | 疾病/病症 | 分期 |
|---|---|---|
| Psychiatric disorders | Substance-induced psychotic disorder | ✓ Approved |
Zou Song-Song SS, Chen Li-Li LL, Cui Min M
[This corrects the article DOI: 10.3389/fimmu.2026.1852083.].
Asra Ridho R, Browne Wesley R WR, Male Louise L, Jones Alan M AM
Phenothiazine (PTZ)-based antipsychotic drugs are extensively metabolised in vivo, with S-oxidation representing a major metabolic pathway. Herein, we report the application of an electrosynthetic (ES) S-oxidation strategy to three distinct classes of PTZ-based drug analogues: amino alkyl, piperidine, and piperazine-containing derivatives. The sulfoxide metabolites of the amino alkyl-containing PTZs, including chlorpromazine sulfoxide (2a, 68%), promazine sulfoxide (3a, 34%), triflupromazine sulfoxide (4a, 36%), and promethazine sulfoxide (5a, 11%), were generated under mild, constant-current conditions. For the piperidine-containing PTZs, electrooxidation of thioridazine (6) selectively afforded mesoridazine (7, 15%), while further S-oxidation of 7 at the PTZ ring system yielded the novel bis-sulfoxide 7a (3%). The piperazine-containing PTZs trifluoperazine (8) and fluphenazine (9) provided sulfoxide metabolites 8a (9%) and 9a (5%), alongside unprecedented ring-opened products 8b (1%) and 9b (2%) arising from electrochemical cleavage of the piperazine ring. Two distinct ring-opening mechanisms via decarboxylation (N-demethylation, Shono-type pathway) and via α-cleavage (neighbouring group participation) are proposed. Cyclic voltammetry confirmed successful S-oxidation through the characteristic disappearance of the first oxidation wave in all metabolite products. The methodology was further extended to thioether-containing active pharmaceutical ingredients (APIs) extracted from commercial dosage forms.
Jin Yan-Ting YT, Zhang Tian-Yu TY, Xiang Chang-Cheng CC, Ma Cai-Yi CY et al.
Bipolar Disorder (BD) is a severe psychiatric condition with high heritability and clinical heterogeneity. Despite numerous genetic variants linked to BD through Genome- Wide Association Studies (GWAS), the molecular mechanisms and effective therapeutic targets remain unclear. This study aims to identify potential therapeutic targets for BD using a systematic approach. In this study, we performed a systematic druggable genome-wide Mendelian Randomization (MR) analysis to identify potential therapeutic target genes for BD. We integrated large-scale GWAS data, expression Quantitative Trait Loci (eQTL) datasets, and druggable gene resources to construct a set of 6,888 potential druggable genes. MR methods were applied to infer causal relationships between these genes and BD. Additionally, Protein-Protein Interaction (PPI) network analysis, Gene Ontology (GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to explore the biological functions and pathways involved. Drug enrichment analysis was performed to assess the association between identified genes and approved psychiatric drugs, while Bayesian colocalization analysis was used to provide evidence for causal genetic signals underlying potential druggable targets. Our MR analysis revealed 34 genes with significant causal associations with BD. These genes were found to be predominantly involved in immune regulation, neuro-metabolic processes, and oxidative stress-related pathways. Drug enrichment analysis identified a close association between these genes and several approved psychiatric drugs, including trifluoperazine, clozapine, and alprazolam. Further, Bayesian colocalization analysis provided strong evidence for GSTM1 and CD52 as potential druggable targets for BD, suggesting that their gene expression shares causal genetic signals with disease susceptibility. Our findings support previous studies linking immune dysregulation to BD, with the identified genes enriched in immune-metabolic and oxidative stress pathways. A key limitation is the reliance on GWAS data primarily from European cohorts, which may limit the generalizability to other populations. This study prioritizes candidate druggable genes for BD through integrative analysis of GWAS, eQTL, MR, drug enrichment, and colocalization evidence. Our findings provide insights into BD-related molecular mechanisms and suggest potential avenues for target prioritization and drug repurposing research.
Singh Shaurya S, Shenoy Sonia S, Praharaj Samir Kumar SK
Although antipsychotic polypharmacy (APP) is not recommended for the treatment of schizophrenia, it remains a common clinical practice. While APP is generally presumed to be associated with a higher burden of adverse effects, the current evidence remains inconclusive. This study compared the adverse effects experienced by patients with schizophrenia (excluding those receiving clozapine) treated with antipsychotic monopharmacy (APM) or APP using both subjective and objective assessments. This cross-sectional study included 114 patients with schizophrenia (56 receiving APM and 58 receiving APP). Spontaneously reported adverse effects, including their number and type, were recorded. Objective adverse effects were assessed using the Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS), Simpson-Angus Scale (SAS), Barnes Akathisia Rating Scale (BARS), and Abnormal Involuntary Movement Scale (AIMS). No significant differences were observed between the APM and APP groups on the overall subjective or objective measures of adverse effects. However, headache (P = 0.04), difficulty concentrating (P = 0.01), constipation (P = 0.01), restlessness (P = 0.01), and insomnia (P = 0.006) were reported significantly more frequently in the APP group. Compared with the APM group, patients receiving APP had a significantly longer duration of illness (P = 0.004; d = 0.55), lower treatment adherence (P = 0.02; d = 0.25), a higher total chlorpromazine-equivalent dose (P < 0.001; d = 1.21), and a higher rate of trihexyphenidyl use (P = 0.01; φ = 0.23). Overall adverse effects were comparable between the APM and APP groups. However, APP was associated with higher antipsychotic and trihexyphenidyl use; more insomnia, restlessness, constipation, and difficulty concentrating; and poorer treatment adherence.
Malik Omar O, Rodriguez-Fernandez Jorge J, Yakubu Aliu Opeyemi AO, Farrag Wedad W et al.
The rise of antimicrobial resistance and limited development of new antibiotics have increased interest in drug repurposing. Preclinical evidence suggests that certain psychotropic drugs, including trifluoperazine (TFP) and amoxapine (AXPN), possess antimicrobial or immunomodulatory properties. However, their effects on infection risk in clinical populations are largely unknown. This study evaluated whether TFP or AXPN use is associated with altered risks of infectious illnesses, systemic inflammation, and mortality compared to patients not taking antidepressants. This retrospective cohort study utilized TriNetX, a federated network of de-identified electronic health records from over 75 million patients. Patients prescribed TFP, AXPN, fluoxetine, or no antidepressants/antipsychotics (general control) were assigned to mutually exclusive cohorts. Age- and sex-matched comparisons were conducted for four groups. Assessed outcomes included bacterial and viral infections (e.g., Clostridioides difficile), severe acute respiratory syndrome coronavirus 2, an etiological agent of COVID-19, as well as for pneumonia and sepsis, inflammatory markers (C-Reactive Protein, Erythrocyte Sedimentation Rate, ferritin, and procalcitonin), Intensive Care Unit admission, and mortality. Risk ratios (RR), odds ratios (OR), 95% confidence intervals, and Kaplan-Meier survival analyses were performed for significant findings. Overall, 2,177 TFP and 834 AXPN patients met the inclusion criteria. TFP was associated with significantly lower rates of ENT/dental infections across all three age groups compared with general controls (RR 0.316-0.405, all p ≤ 0.002). It was also consistently associated with increased leukocytosis across all age strata. Reduced COVID-19 incidence was observed primarily in older adults (70-90 years) versus general controls. AXPN showed fewer associations overall, with a significant reduction in C. difficile infection (RR 0.458, p = 0.025) and lower leukocytosis (RR 0.685, p = 0.012) in the 70-90 age group compared with fluoxetine. Most other outcomes, including pneumonia, sepsis, and other inflammatory markers, did not differ significantly when compared to general control or fluoxetine groups. These exploratory findings identify potential signals linking TFP and AXPN to infection susceptibility. Given the study design, these observations are hypothesis-generating and require confirmation in future prospective studies.
Hakami Zanjani Ali Asghar AA
This mini-review examines how molecular dynamics simulations reshape the view of annexin-mediated plasma membrane repair from simple recruitment to coupled protein-membrane states. Molecular dynamics simulations show that annexin-induced curvature is shaped by oligomerization, cholesterol, and anionic lipid chemistry, while engineering normally non-trimerizing annexin A3 into a trimer-forming state demonstrates that curvature generation alone does not ensure repair competence. Membrane-active perturbants such as trifluoperazine further suppress repair by altering bilayer thickness, lipid packing, phosphatidylserine mobility, and annexin binding. These findings shift the question from whether annexins arrive to how protein-membrane states generate repair-relevant remodeling.
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