Fluphenazine (dose) for people with schizophrenia

Turk, Tarek; Yafi, Ruba Zuhri; Namous, Lubaba O; Alkhaledi, Ahmad; Salahia, Sami; Haider, Al Yaman; Essali, Adib

doi:10.1002/14651858.cd012848

Cited by 2 publications

(2 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We demonstrate here that fluphenazine reduces GCH1 and BH4 in DRG cultures and in sensory neurons after sciatic nerve injury in mice. Moreover, we show that fluphenazine treatment markedly alleviated pain hypersensitivity after nerve injury in mice, using a dose that is comparable to that used in patients (0.01 mg/kg daily intraperitoneally in our study in mice versus the range 0.006 to 0.125 mg/kg orally used in patients) ( 56 ). Side effects of fluphenazine treatment include movement disorders and depression ( 57 – 59 ).…”

Section: Discussionmentioning

confidence: 63%

Phenotypic drug screen uncovers the metabolic GCH1/BH4 pathway as key regulator of EGFR/KRAS-mediated neuropathic pain and lung cancer

Cronin

Tejada

et al. 2022

Sci. Transl. Med.

View full text Add to dashboard Cite

Increased tetrahydrobiopterin (BH4) generated in injured sensory neurons contributes to increased pain sensitivity and its persistence. GTP cyclohydrolase 1 (GCH1) is the rate-limiting enzyme in the de novo BH4 synthetic pathway, and human single-nucleotide polymorphism studies, together with mouse genetic modeling, have demonstrated that decreased GCH1 leads to both reduced BH4 and pain. However, little is known about the regulation of Gch1 expression upon nerve injury and whether this could be modulated as an analgesic therapeutic intervention. We performed a phenotypic screen using about 1000 bioactive compounds, many of which are target-annotated FDA-approved drugs, for their effect on regulating Gch1 expression in rodent injured dorsal root ganglion neurons. From this approach, we uncovered relevant pathways that regulate Gch1 expression in sensory neurons. We report that EGFR/KRAS signaling triggers increased Gch1 expression and contributes to neuropathic pain; conversely, inhibiting EGFR suppressed GCH1 and BH4 and exerted analgesic effects, suggesting a molecular link between EGFR/KRAS and pain perception. We also show that GCH1/BH4 acts downstream of KRAS to drive lung cancer, identifying a potentially druggable pathway. Our screen shows that pharmacologic modulation of GCH1 expression and BH4 could be used to develop pharmacological treatments to alleviate pain and identified a critical role for EGFR-regulated GCH1/BH4 expression in neuropathic pain and cancer in rodents.

show abstract

Section: Discussionmentioning

confidence: 63%

Phenotypic drug screen uncovers the metabolic GCH1/BH4 pathway as key regulator of EGFR/KRAS-mediated neuropathic pain and lung cancer

Cronin

Tejada

et al. 2022

Sci. Transl. Med.

View full text Add to dashboard Cite

show abstract

“…Up until today (28 February 2020), this classification effort has detected new comparisons for review titles, new classes of drugs and new qualifiers from existing RCTs. These discoveries were assessed by Cochrane editors and led to start and, in some cases, accomplishment of at least 14 Cochrane reviews: six on qualifiers (Abbas et al, 2017; Hanafi et al, 2017; Latifeh et al, 2019; Turk, Alkhatib, et al, 2017; Turk, Zuhri Yafi, et al, 2017; Turkmani et al, 2019), one on a class of drugs (Karl et al, 2018) and nine on comparing two drugs (Bazrafshan et al, 2015; Chattopadhyay et al, 2016; Eslami Shahrbabaki et al, 2018; Ibragimov et al, 2019; Mazhari et al, 2017; Nikvarz et al, 2017; Nur & Adams, 2016; Schmidt et al, 2019; Zare & Bazrafshan, 2017).…”

Section: Discussionmentioning

confidence: 99%

Classification of all pharmacological interventions tested in trials relevant to people with schizophrenia: A study‐based analysis

Shokraneh

Adams

2021

Health Info Libraries J

View full text Add to dashboard Cite

Background Systematic reviewing is a time‐consuming and resource‐intensive process. Information specialists are maintaining study‐based registers to facilitate efficient conduct of systematic reviews. Classification of study‐level meta‐data ‐such as interventions –can result in much more accurate searches, saving time in the early steps of systematic reviewing. Objective To classify all pharmacological interventions from all schizophrenia trials. Methods We used Cochrane Schizophrenia's Study‐based Register as the source of trials, Emtree and MeSH for synonyms, AdisInsight and http://CT.gov for research drugs and WHO ATC for marketed drugs. Results One third of tested interventions on patients with schizophrenia are pharmacological (816; belonging to 106 clinical classes) with antipsychotic drugs being the most researched (15.1%). Only 528 of these medications are listed in WHO ATC. Around one third of these drug interventions are seen only in research (236; from 21 pharmacological/biochemical classes). Within the pharmacological interventions, we identified 28 ‘qualifiers’ including dose, route and timing of drug delivery. Conclusion Identification and classification of pharmacological interventions from trials require use of many sources of information none of which are inclusive of all drugs. Limitations of each source are helpful to understand. Classification of non‐pharmacological interventions is now a priority for clinical and information scientists and professionals.

show abstract

Fluphenazine (dose) for people with schizophrenia

Abstract: This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:To assess and compare the efficacy and safety of the different doses of fluphenazine for people with schizophrenia.

Cited by 2 publications

References 38 publications

Phenotypic drug screen uncovers the metabolic GCH1/BH4 pathway as key regulator of EGFR/KRAS-mediated neuropathic pain and lung cancer

Phenotypic drug screen uncovers the metabolic GCH1/BH4 pathway as key regulator of EGFR/KRAS-mediated neuropathic pain and lung cancer

Classification of all pharmacological interventions tested in trials relevant to people with schizophrenia: A study‐based analysis

Contact Info

Product

Resources

About