Targeting Angiogenesis With Fluphenazine-Zinc Oxide Nanoconjugates: A Potential Mechanism for Improving Antipsychotic Efficacy

DASARI, NAGASEN; BALLA, SUJIYA; KONDRAPU, PYDIRAJU; GUMMADI, RAMAKRISHNA; SURADA, NOOKARAJU; KONDRU, UMA MAHESWARI; PINDIPROLU, SAI KIRAN S. S.

doi:10.22159/ijap.2023v15i5.48317

Cited by 3 publications

(1 citation statement)

References 24 publications

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“…Atypical antipsychotics are also known as second-generation antipsychotics. Some of the examples include aripiprazole, quetiapine, olanzapine, and risperidone [6].…”

Section: Introductionmentioning

confidence: 99%

Effects of Neuroleptics With or Without Anti-Cholinergics Among Schizophrenic Patients of South Gujarat

SODHA,

SHETH,

YADAV

et al. 2024

Asian J Pharm Clin Res

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Objective: Neuroleptics (or anti-psychotics) indicated for the treatment of schizophrenia have significant dose-limiting extra-pyramidal side effects (EPS). Literature suggests limited evidence for the efficacy of anticholinergics in the treatment of neuroleptic-induced EPS. Thus, the present study was conducted to understand the effects of anti-cholinergics on EPS among schizophrenics already on neuroleptics (typical and atypical). Methods: This prospective, cross-sectional, observational study was conducted at a tertiary care teaching hospital in South Gujarat for 15 months. A total of 200 participants were included based on selection criteria and distributed equally among four groups (A, B, C, and D) of 50 participants each. The collected data were analyzed for sociodemographic profile, current treatment regimen, type of neuroleptic drug, present complaints of EPS, and addition of any anti-cholinergic agent. An abnormal involuntarily movement scale score was used for examining movement disorders in all study participants. Descriptive statistical analysis was done using Microsoft Excel 2019 and IBM SPSS software version 28, and p<0.05 was considered statistically significant. Results: Hundred patients who were prescribed typical neuroleptics were divided into groups A (with anti-cholinergic) and B (without anti-cholinergic), whereas the remaining 100 patients being prescribed atypical neuroleptics were divided into groups C (with anti-cholinergic) and D (without anti-cholinergic) by simple randomization. The majority of 56% were young adults (18–35 years) with an overall male pre-ponderance (2.14:1). Out of 50 participants in both groups A and B, a higher number of group B participants experienced tremors, rigidity, difficulty in movements, and tardive dyskinesia (TD) (48/50 vs. 30/50, 36/50 vs. 6/50, 24/50 vs. 1/50, 36/50 vs. 19/50) as compared to group A, respectively. Similar results were noted with groups C and D, where a higher number of group D participants experienced tremors, rigidity, difficulty in movements, and tardive dyskinesia (TD) (15/50 vs. 5/50, 11/50 vs. 3/50, 18/50 vs. 2/50, and 16/50 vs. 4/50, respectively). All the results were statistically significant (p<0.05). Conclusion: There was a significant reduction in EPS among schizophrenia patients who were prescribed atypical over typical neuroleptics. The addition of one anticholinergic to the drug regimen also significantly reduced the frequency of EPS in schizophrenia patients.

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“…Atypical antipsychotics are also known as second-generation antipsychotics. Some of the examples include aripiprazole, quetiapine, olanzapine, and risperidone [6].…”

Section: Introductionmentioning

confidence: 99%

Effects of Neuroleptics With or Without Anti-Cholinergics Among Schizophrenic Patients of South Gujarat

SODHA,

SHETH,

YADAV

et al. 2024

Asian J Pharm Clin Res

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Managing high disease burden: a study of medication rationality in diabetes and hypertension in Andhra Pradesh

Dasari,

Ahmed,

Panda

et al. 2024

J Diabetes Metab Disord

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Dual TTK/PLK1 inhibition has potent anticancer activity in TNBC as monotherapy and in combination

Zanini,

Forster-Gross,

Bachmann

et al. 2024

Front. Oncol.

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BackgroundThreonine tyrosine kinase (TTK) and polo-like kinase 1 (PLK1) are common essential kinases that collaborate in activating the spindle assembly checkpoint (SAC) at the kinetochore, ensuring appropriate chromosome alignment and segregation prior to mitotic exit. Targeting of either TTK or PLK1 has been clinically evaluated in cancer patients; however, dual inhibitors have not yet been pursued. Here we present the in vitro and in vivo characterization of a first in class, dual TTK/PLK1 inhibitor (BAL0891).MethodsMechanism of action studies utilized biochemical kinase and proteomics-based target-engagement assays. Cellular end-point assays included immunoblot- and flow cytometry-based cell cycle analyses and SAC integrity evaluation using immunoprecipitation and immunofluorescence approaches. Anticancer activity was assessed in vitro using cell growth assays and efficacy was evaluated, alone and in combination with paclitaxel and carboplatin, using mouse models of triple negative breast cancer (TNBC).ResultsBAL0891 elicits a prolonged effect on TTK, with a transient activity on PLK1. This unique profile potentiates SAC disruption, forcing tumor cells to aberrantly exit mitosis with faster kinetics than observed with a TTK-specific inhibitor. Broad anti-proliferative activity was demonstrated across solid tumor cell lines in vitro. Moreover, intermittent intravenous single-agent BAL0891 treatment of the MDA-MB-231 mouse model of TNBC induced profound tumor regressions associated with prolonged TTK and transient PLK1 in-tumor target occupancy. Furthermore, differential tumor responses across a panel of thirteen TNBC patient-derived xenograft models indicated profound anticancer activity in a subset (~40%). Using a flexible dosing approach, pathologically confirmed cures were observed in combination with paclitaxel, whereas synergy with carboplatin was schedule dependent.ConclusionsDual TTK/PLK1 inhibition represents a novel approach for the treatment of human cancer, including TNBC patients, with a potential for potent anticancer activity and a favorable therapeutic index. Moreover, combination approaches may provide an avenue to expand responsive patient populations.

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Targeting Angiogenesis With Fluphenazine-Zinc Oxide Nanoconjugates: A Potential Mechanism for Improving Antipsychotic Efficacy

Cited by 3 publications

References 24 publications

Effects of Neuroleptics With or Without Anti-Cholinergics Among Schizophrenic Patients of South Gujarat

Effects of Neuroleptics With or Without Anti-Cholinergics Among Schizophrenic Patients of South Gujarat

Managing high disease burden: a study of medication rationality in diabetes and hypertension in Andhra Pradesh

Dual TTK/PLK1 inhibition has potent anticancer activity in TNBC as monotherapy and in combination

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