P2/3, N=30, Recruiting, M.D. Anderson Cancer Center | Active, not recruiting --> Recruiting | N=11 --> 30

P1, N=32, Recruiting, Capital Medical University | Not yet recruiting --> Recruiting

We verify the structure using mutagenesis and confirm that the conformation corresponds to the active state of the receptor. Subsequent study of TrkB interaction with the antidepressant drug fluoxetine, and the antipsychotic drug chlorpromazine, provides a clear self-consistent model, describing the mechanism by which fluoxetine activates the receptor by binding to its transmembrane domain.

P1, N=32, Not yet recruiting, Capital Medical University

Previous studies have shown that chlorpromazine (CPZ) can inhibit YAP1 expression...Collectively, our findings indicate that FOXP3 competitively binds TEAD4 to regulate YAP1 localization in the nucleus and cytoplasm to suppress NPC progression. Consequently, FOXP3 may be a prognostic indicator for HNSCC.

P=N/A, N=338, Suspended, The Affiliated Hospital of Shandong Second Medical University; The Affiliated Hospital of Shandong Second Medical University | Not yet recruiting --> Suspended

P=N/A, N=200, Completed, Central South University | Recruiting --> Completed

Chlorpromazine potentiates the cytotoxic effects of the alkylating agent temozolomide through a mechanism involving downregulation of Cx43 expression and disruption of the cell cycle arrest essential for DNA repair processes. This finding suggests that chlorpromazine may be a potential therapeutic strategy to overcome TMZ resistance in GBM cells by inhibiting their DNA repair mechanisms.

P3, N=0, Withdrawn, Centre Hospitalier St Anne | N=40 --> 0 | Unknown status --> Withdrawn

P2/3, N=11, Active, not recruiting, M.D. Anderson Cancer Center | Enrolling by invitation --> Active, not recruiting | N=150 --> 11

This is one of the few published cases of COVID-19 associated persistent hiccups, occurring more than a month after the initial presentation. Most of the published cases report hiccups occurring in the acute COVID-19 period. Consequently, hiccups occurring in the post-acute COVID-19 period may not be attributable to COVID-19. This case has highlighted the need to consider post-acute COVID-19 in the differential diagnosis of persistent hiccup.

Taurine and COQ-10 alone notably improved the antioxidant/anti-inflammatory status relative to controls. Among other mechanisms, taurine and COQ-10 abated CPZ-induced hematological deficiencies, via decreased serum levels of oxidative stress, and pro-inflammatory cytokines release, with increased antioxidants and anti-inflammation function.

Based on our findings, a mechanism of cell death was not able to be established due to lack of cleaved caspase-3 expression. Capable of bypassing many aspects of the lengthy, costly, and difficult cancer drug approval process, chlorpromazine and prazosin deserve further investigation for use in conjunction with traditional chemotherapeutics.

Endocytosis inhibitors identified that Monensin and Chlorpromazine hydrochloride significantly reduced MM-ZC internalization...Overall, the current study provides valuable insights into the cellular uptake and intracellular trafficking of MM-ZC in myeloma cells. Identifying these mechanisms and molecular players involved in MM-ZC uptake contributes to a better understanding of the delivery and potential applications of cell-specific Zip-Codes in gene delivery and drug targeting in cancer research.

Mechanistically, the direct binding of JX57 to GRP75 impairs the structure of the mitochondria-associated endoplasmic reticulum membrane and disrupts the endoplasmic reticulum-mitochondrial calcium homeostasis, resulting in a mitochondrial energy crisis and AMP-activated protein kinase activation. Taken together, these findings highlight GRP75 as a potential prognostic biomarker and direct therapeutic target in endometrial cancer and suggest that the chlorpromazine derivative JX57 can potentially be a new therapeutic option for endometrial cancer.

In this phase II clinical trial, we evaluated the addition of chlorpromazine to temozolomide in the adjuvant phase of the standard first-line therapeutic protocol in patients with unmethylated MGMT gene promoter. These findings provide proof-of-concept for the potential of adding CPZ to standard TMZ treatment in GBM patients with unmethylated MGMT gene promoter. https://clinicaltrials.gov/study/NCT04224441, identifier NCT04224441.

The effect of CPZ can be epitomized as an inhibition of the Warburg effect and thus malignancy in GBM cells, while sparing RPE-1 cells. These preclinical data enforce the rationale that allowed us to investigate the role of CPZ in GBM treatment in a recent multicenter Phase II clinical trial.

P1, N=70, Completed, Whanin Pharmaceutical Company | .

P1/2, N=266, Completed, Otsuka Pharmaceutical Development & Commercialization, Inc. | Phase classification: P1b --> P1/2

6,9). The addition of Chlorpromazine to temozolomide was well tolerated in newly diagnosed Glioblastoma unmethylated patients, with promising impact on outcome measures.

P2/3, N=70, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jun 2023 --> Jun 2025

P1, N=15, Recruiting, Mohammed Milhem | Trial completion date: Jun 2025 --> Jul 2024 | Trial primary completion date: Jun 2023 --> Jul 2024

Despite current treatment options such as surgery, radiotherapy, and the use of temozolomide and bevacizumab, it is considered incurable...Typical antipsychotics include chlorpromazine, trifluoperazine, and pimozide...Olanzapine and Quetiapine are examples of atypical antipsychotics, a category that was created later...These include NF-B suppression, cyclin deregulation, and -catenin phosphorylation, among others. This review will delve deeper into the polypharmacological, the multiple effects of antipsychotics in the treatment of GBM, and an outlook for the field's future progression.

In this study, the antipsychotic drug chlorpromazine was characterized as an LSD1 inhibitor (IC = 5.135 μM), and a series of chlorpromazine derivatives were synthesized...An in vivo study confirmed that compound 3s can inhibit MFC cell proliferation without significant toxicity in immunocompetent mice. Taken together, our findings indicated that the novel LSD1 inhibitor 3s tethering a phenothiazine scaffold may serve as a lead compound for further development to activate T-cell immunity in gastric cancer.

Amisulpride and/or aripiprazole have a favorable role in turning on Shh-pathway with subsequent beneficial cognitive and neurogenesis effects.

DRD4 reduced expression in breast CSCs or its inhibition by Haloperidol favors CSCs-pool expansion. DRD4 inhibition can also reduce cell migration, indicating that DRD4 plays different roles in stem and non-stem breast cancer cells.

CPZ is administered orally at a dose of 50 mg/day – GG 1-28 – of every cycle of the adjuvant treatment with TMZ. At present, 53 patients out of 60 patients planned have been enrolled, without relevant toxicity.

When utilized in combination with trametinib (a MEK inhibitor), dabrafenib (an RAF inhibitor), and everolimus (an mTOR inhibitor), CPZ suppressed the growth of PC9ZD cells cooperatively with everolimus but not with trametinib or dabrafenib. However, after CPZ treatment, EGFR was unevenly distributed in the cells, and colocalization with the early endosome marker Rab5 and EEA1 became more apparent, indicating that CPZ disrupted the intracellular transport of EGFR. These results suggest that CPZ has therapeutic potential for NSCLC with mutated EGFR by a novel mechanism different from conventional TKIs alone or in combination with other agents.

We conclude that only aripiprazole, but not olanzapine, protects liver cells against oxidative stress. This finding could be relevant for schizophrenia patients with high-oxidative-stress-risk lifestyles and needs to be validated in vivo.

Aripiprazole and IR-induced apoptosis were accompanied by an increase in reactive oxygen species and was almost completely suppressed by the addition of the antioxidant, N-acetylcysteine. Finally, aripiprazole greatly sensitized xenograft tumors to IR at doses that did not affect tumor growth. Taken together, these results suggest that aripiprazole could be considered a potent radiosensitizer for head and neck cancer.

The ranking in order of Hyperprolactinemia presented by these authors: Paliperidone > Risperidone > Lurasidone > Ziprasidone > Iloperidone > Olanzapine > Asenapine > Placebo > Quetiapine > Aripiprazole...Cabergoline is preferable to Bromocriptine...Another type of treatment: Alternative and symptomatic management can also be attempted. Estrogens or testosterone for hypogonadism and/or decreased BMD, PDE5 inhibitors for erectile dysfunction, promoting healthy diet and physical exercise, avoiding tobacco and alcohol, for amenorrhea>6 months OCPs can be given to prevent osteoporosis, If low Vitamin D levels, then supplementation etc Psychiatrists need to work corroboratively with other specialties of Medicine and keep abreast of recent evidence base to manage this problem.

CPZ is administered orally at a dose of 50 mg/day – GG 1-28 – of every cycle of the adjuvant treatment with TMZ. At present, 38 patients out of 41 patients planned have been enrolled.

These findings indicated that repurposing CPZ is a novel treatment strategy for CRC patients.

Relative to wildtype MCF10A cells, CDH1 MCF10A cells showed significantly greater sensitivity to several drugs targeting these processes, including the autophagy inhibitor chloroquine, the endocytosis inhibitors chlorpromazine and PP1, and the sphingosine kinase 1 inhibitor PF-543. Synthetic lethality was confirmed in both gastric and mammary organoid models of CDH1 loss, derived from CD44-Cre/Cdh1/tdTomato mice. Collectively, these results suggest that both sphingolipid metabolism and vesicle trafficking represent previously unrecognised druggable vulnerabilities in CDH1-null cells and may lead to the development of new therapies for HDGC.

These GPCRs play a critical role in the treatment of cardiovascular disease, diabetes, cancer, and neurological disorders. The results of this study may thus provide novel preventive and therapeutic strategies for noncommunicable diseases (NCDs).

CPZ is administered orally at a dose of 50 mg/day – GG 1-28 – of every cycle of the adjuvant treatment with TMZ. At present, 28 patients out of 41 patients planned have been enrolled, without relevant toxicity.

This discrepancy could be central in explaining the lethal effects of the drug on GBM cells and the relatively scarce cytotoxicity toward normal tissues attributed to this compound. The data presented here offer support to the multicenter phase II clinical trial we have undertaken, which consists of the addition of CPZ to first-line treatment of GBM patients carrying a hypo- or un-methylated MGMT gene, i.e. those characterized by intrinsic resistance to temozolomide.

There was a similar increase in protein levels of P21, P27 and SIPR2 in OCI-LY3 and TMD8 cells after 24 hours of treatment (P<0.05) . Chlorpromazine hydrochloride at a specific concentration may inhibit the proliferation of ABC diffuse large B lymphoma cells by promoting the expression of S1PR2, and promote cell apoptosis and G1 phase cell cycle arrest.

Moreover, the colocalization of LC3 with lysosomal-associated membrane protein 1 (LAMP1), a lysosome marker, was also suppressed after TFP treatment, suggesting that TFP might block the fusion of autophagosomes with lysosomes, which led to autophagosome accumulation. Taken together, our data highlight the potential of repurposing TFP as a new adjuvant drug for treating melanoma patients with brain, lung, and bone metastases.

Aripiprazole showed a cytotoxicity (IC50 = 12.1 ± 0.40 μM) to MCF-7 cells, comparable to the standard anticancer drug doxorubicin (IC50 = 1.25 ± 0.34 μM). The drug was also able to significantly increase the nuclear condensation, and modulated the expression of certain genes involved in breast cancer, such as caspases 3, and 9, BAK-1, C-MYC, BCL2L1, BCL-10, and BCL-2. Further studies are needed to explore the effect of aripiprazole on intrinsic and extrinsic pathways of apoptosis in cancer cells.