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trifluoperazine + trihexyphenidyl (Fluhex forte / Fluhex / Fluhexette)

✓ Approved

A. N. Pharmacia Laboratories · CHRM1 · Small Molecule

What is trifluoperazine + trihexyphenidyl?

trifluoperazine + trihexyphenidyl is a small molecule developed by A. N. Pharmacia Laboratories. It is approved for therapeutic indications via oral (po).

Drug Profile

Brand NamesFluhex forte, Fluhex, Fluhexette
CompanyA. N. Pharmacia Laboratories
Drug ClassSmall Molecule
Molecular TargetCHRM1
RouteOral (PO)
StatusApproved
Sources: ClinicalTrials.gov, A. N. Pharmacia Laboratories

Mechanism of Action

Molecular Targets

trifluoperazine + trihexyphenidyl acts on 1 molecular target:

CHRM1cholinergic receptor muscarinic 1 (M1, HM1)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

trifluoperazine + trihexyphenidyl is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Psychiatric disordersSubstance-induced psychotic disorder✓ Approved

Related Research Articles

PubMedCureus2026-11-10

Severe Motor Deterioration of Young-Onset Parkinson's Disease in Pregnancy Following Medication Rationalisation: A Case Report.

Naing Ei Ei P EEP, Ko Ko Naw Phu N NPN, Phyu Mya K MK

Parkinson's disease (PD) in pregnancy is rare, and there are no agreed guidelines for its management. We report a 34-year-old primigravida with a three-year history of young-onset PD who presented at eight weeks' gestation with an unplanned pregnancy. She had previously tolerated levodopa poorly, with nausea and early peak-dose dyskinesia, and before conception her symptoms were reasonably controlled on amantadine, selegiline and procyclidine. Because of the potential teratogenicity of amantadine and limited safety data for the other agents, her treatment was changed to co-careldopa (carbidopa/levodopa) with domperidone. Her condition deteriorated soon after the switch. Despite stepwise increases in levodopa to 400-450 mg/day, by 31 weeks she was wheelchair-dependent, with severe peak-dose dyskinesia alternating with "off" periods and freezing, and she relied on her husband for feeding and personal care. Other drug options and deep brain stimulation were deferred until after delivery. Her care involved neurology, obstetric medicine, obstetric anaesthesia, safeguarding midwives, physiotherapy and occupational therapy, and she received thromboprophylaxis for immobility. She presented in spontaneous labour at 37+5 weeks and underwent a category 2 caesarean section under general anaesthesia, as constant tremor precluded neuraxial anaesthesia. Estimated blood loss was 750 mL. Her daughter had Apgar scores of 4, 7 and 9 at 1, 5 and 10 minutes, respectively, and weighed 2250 g (3.4th centile). Postpartum, dyskinesia and tremor temporarily prevented her from holding her baby, and trihexyphenidyl was started; her symptoms were unchanged five weeks after delivery. In young-onset PD, withdrawal of an effective pre-pregnancy regimen may be followed by significant functional decline, and previous levodopa intolerance may be a warning sign. This case highlights the importance of pre-conception counselling, early multidisciplinary planning and postnatal support.

PMID 43006005
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PubMedbioRxiv : the preprint server for biology2026-11-06

Cancer cells hijack mitochondria from Bhlhe40+ T cells for immune evasion.

Hu Hailong H, Tan Yuhao Y, Shkundina Irina I, Madnick Richard R et al.

Cancer cells hijack mitochondria from T cells via tunneling nanotubes (TNTs) to promote immune evasion, yet the underlying mechanisms of mitochondrial-loss remain poorly understood. Here, through targeted screening of relevant genes, we demonstrated that CD38 is a potent regulator of TNT formation through interaction with its cognate ligand, CD31. Conditional knockdown of Cd38 in murine models leads to CD8 + T cell-dependent tumor shrinkage. Single-cell RNA sequencing of tumor-infiltrating T cells revealed that cancer cells preferentially target the Bhlhe40+ effector subset. Bhlhe40 is a transcription factor that upregulates the expression of S100a4, a reported chemoattractant of nanotubes. Bhlhe40 upregulation creates mitochondrial-loss vulnerability for tumor neoantigen-specific T cells. Dual mitochondria transfer blockade with Cd38 knockdown and S100a4 inhibitor trifluoperazine markedly suppressed tumor growth. Collectively, our findings identified the Bhlhe40-S100a4 cascade as a critical regulator of cancer/T cell mitochondrial transfer, providing insights for the development of new cancer immunotherapies.

PMID 42990284
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PubMedRisk management and healthcare policy2026-11-03

Development and Internal Validation of a Risk Prediction Model for Clozapine-Induced Gastrointestinal Hypomotility: A Single-Center Retrospective Cohort Study.

Tian Feng-Jun FJ, Zhang Yong Y, Tian Jiang-Ke JK, Cui Hong-Li HL et al.

To develop and internally validate a prediction model for a first episode of clozapine-induced gastrointestinal hypomotility (CIGH) in clozapine-treated psychiatric inpatients. In this single-center retrospective cohort study, 1,426 adults with schizophrenia, schizoaffective disorder or bipolar disorder who had received clozapine for at least 4 weeks and were admitted to the Department of Psychiatry of Beijing United Family Rehabilitation Hospital between January 2019 and December 2025 were included. The index date was defined as the date of the current psychiatric admission, and all predictors were measured at or before that date. The outcome was a first CIGH event within 90 days, defined as paralytic ileus or intestinal obstruction, severe constipation requiring pharmacological intervention, or fecal impaction. Predictors were selected using LASSO regression, and the model was constructed with multivariable logistic regression. Performance was assessed using the area under the receiver operating characteristic curve (AUC), the calibration curve and decision curve analysis, and internal validation used 1,000 bootstrap resamples. Static and interactive (Shiny) nomograms were developed. CIGH occurred in 356 of 1,426 patients (24.96%). Six predictors were retained: age ≥60 years (OR 1.469, 95% CI 1.031-2.094), BMI <24 kg/m2 (OR 1.699, 95% CI 1.099-2.628), daily clozapine dose ≥300 mg (OR 2.276, 95% CI 1.531-3.384), clozapine treatment duration ≥5 years (OR 2.309, 95% CI 1.431-3.725), concomitant use of trihexyphenidyl (OR 3.322, 95% CI 2.291-4.818) and predominantly bedridden status (OR 2.608, 95% CI 1.817-3.744). Discrimination was moderate (AUC 0.731, 95% CI 0.694-0.768; bootstrap-corrected AUC 0.718), calibration was acceptable, and decision curve analysis indicated net benefit across threshold probabilities of 15%-70%. This internally validated model provides a non-invasive aid for stratifying 90-day CIGH risk in clozapine-treated psychiatric inpatients and for structuring gastrointestinal monitoring. External validation and prospective evaluation of clinical utility are required before routine implementation.

PMID 42974511
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PubMedSleep medicine2026-10-29

Reduction in reported nightmares during adjunctive trihexyphenidyl treatment in an adolescent: A case report.

Sumitomo Noriko N, Matsui Kentaro K, Tsuru Ayumi A, Matsushima Shun S et al.

Nightmares are a frequent and disabling symptom of posttraumatic stress disorder (PTSD) and may perpetuate fear of sleep, insomnia, and psychiatric deterioration. Evidence for pharmacologic treatment in children and adolescents remains limited. We report a 13-year-old boy with PTSD who reported cessation of persistent nightmares during adjunctive trihexyphenidyl (THP) treatment. Polysomnography showed an apnea-hypopnea index of 9.4/h, with 24.5/h during rapid eye movement (REM) sleep. The patient and his family preferred to prioritize nightmare management and psychiatric care over treatment of obstructive sleep apnea (OSA). THP was started at 1 mg nightly and increased to 2 mg after one week. At one-month follow-up, he reported no nightmares from the first treatment night, and sleep avoidance had resolved despite receiving no OSA treatment. Nightmares recurred within days of abrupt THP discontinuation. Although this course suggests a contribution of THP, we cannot determine whether nightmares ceased or continued without being recalled after awakening. Further studies are needed to clarify its efficacy, safety, dosing, and patient selection.

PMID 42956564
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PubMedBiomolecules2026-10-27

Mechanism-Dependent Effects of the α5 GABAA Receptor Negative Allosteric Modulator Basmisanil on Spatial Memory.

Moraru Miruna Valeria MV, Zugravu Aurelian A, Barbu Aurelia Cristiana AC, Stoleru Smaranda S et al.

Cognitive impairment may arise through multiple pathophysiological mechanisms, including altered GABAergic neurotransmission, cholinergic dysfunction, and neuroinflammation. This study investigated whether basmisanil, a selective negative allosteric modulator of α5-containing GABAA receptors, attenuates spatial memory impairment induced by diazepam, trihexyphenidyl (THP), or lipopolysaccharide (LPS). Adult male Wistar rats were assigned to three experimental models of memory impairment, each comprising four treatment groups (control, inducing agent, basmisanil, and inducing agent plus basmisanil; n = 7/group). Spatial memory was assessed using the two-trial Y-maze paradigm. The primary outcome (Time Index U) was analyzed using two-way factorial general linear models with sensitivity analyses. Significant interactions between the inducing agent and basmisanil were observed in the diazepam and LPS models, indicating attenuation of memory impairment following basmisanil coadministration, whereas no significant interaction was detected in the THP model. The largest estimated recovery effect was observed in the diazepam model, followed by the LPS model and the THP model, although cross-model comparisons were not statistically significant. Basmisanil alone did not enhance baseline memory performance. These findings indicate that the behavioral effects of α5-containing GABAA receptor modulation are mechanism-dependent and support further investigation of selective α5 negative allosteric modulators for benzodiazepine-associated memory impairment.

PMID 42939683
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PubMedJournal of chromatography. B, Analytical technologies in the biomedical and life sciences2026-10-26

From surface water to aquatic macrophytes: Eichhornia crassipes as a complementary matrix for LC-HRMS screening of pharmaceuticals and psychoactive substances.

Arslan Zeynep Z, Bulut Cenk C, Türkmen Zeynep Z

The selection of an appropriate environmental matrix remains a critical factor in HRMS-based suspect screening of emerging contaminants. Although surface water is the most commonly investigated matrix, alternative biological matrices may provide complementary information on contaminant occurrence. In this study, Eichhornia crassipes (water hyacinth) and co-located surface-water samples from the Asi River (Orontes River) were comparatively evaluated as screening matrices for pharmaceuticals and psychoactive substances using an LC-HRMS workflow. Surface-water samples were extracted by solid-phase extraction (SPE), whereas plant tissues were processed using solvent extraction followed by liquid-liquid extraction (LLE) and SPE-based clean-up under different pH conditions to accommodate the complexity of the plant matrix. A suspect-screening approach was applied, and the Schymanski framework was used to assess compound annotation confidence. A total of 19 compounds were detected in E. crassipes, whereas 8 compounds were detected in the corresponding surface-water samples under the applied conditions. The detected substances included compounds confirmed with authentic reference standards (morphine, benzoylecgonine, hydromorphone, codeine, methamphetamine, methylphenidate, and cocaine), as well as probable or tentative annotations including ephedrine, ritalinic acid, venlafaxine metabolites, synthetic cathinones (N-propyl butylone and N-butyl pentylone), PB-22 metabolites, propyphenazone, propofol, and trifluoperazine. Several PB-22 metabolite- and synthetic-cathinone-related features were annotated in E. crassipes, and the plant matrix provided broader qualitative detection coverage in this single sampling event than co-located grab surface-water samples. These findings indicate that E. crassipes may provide complementary information for LC-HRMS-based environmental analysis of pharmaceuticals and psychoactive substances and highlight the importance of matrix selection and matrix-tailored sample preparation in suspect-screening workflows.

PMID 42933069
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