- In vitro and in vivo anti-tumor effects of brexpiprazole, a newly-developed serotonin-dopamine activity modulator with an improved safety profile. [Journal Article]
- OOncotarget 2019 May 28; 10(37):3547-3558
- From the perspective of psycho-oncology, antipsychotics are widely used for patients with cancer. Although some antipsychotic drugs have anti-tumor effects, these antipsychotic drugs are not applicab…
From the perspective of psycho-oncology, antipsychotics are widely used for patients with cancer. Although some antipsychotic drugs have anti-tumor effects, these antipsychotic drugs are not applicable for cancer patients because of their severe side effects. Brexpiprazole, a novel serotonin-dopamine modulator with an improved side effect profile, was developed as a drug that is structurally and pharmacologically related to aripiprazole, which was reported to have anti-cancer effects. However, it remains unknown whether brexpiprazole has anti-cancer effects. In this study, we examined whether brexpiprazole has anti-tumor effects in cancer cells and cancer stem cells (CSCs) of glioblastoma, pancreatic cancer, and lung cancer. Brexpiprazole suppressed cell growth and induced cell death in the cancer cells and the CSCs, and decreased the CSC properties of the CSCs. Brexpiprazole did not exert any cytotoxic effects on non-cancer cells at the anti-cancer effect-inducing concentration. In the cancer cells and the CSCs, brexpiprazole reduced the expression of survivin, an anti-apoptotic protein, whose reduction sensitizes tumor cells to chemotherapeutic reagents. In the preclinical model in which pancreatic CSCs were subcutaneously implanted into nude mice, brexpiprazole suppressed tumor growth, in addition to reducing the expression of Sox2, a marker for CSCs, and survivin. This suggests that brexpiprazole is a promising antipsychotic drug with anti-tumor effects and an improved safety profile.
- Stability Indicating TLC Method for Quantification of Brexpiprazole in Bulk and Its Pharmaceutical Dosage Form and Determination of Content Uniformity. [Journal Article]
- JCJ Chromatogr Sci 2019 May 16
- A sensitive, selective and precise high performance thin layer chromatographic method has been developed and validated for the quantification of Brexpiprazole in bulk drug and in pharmaceutical dosag…
A sensitive, selective and precise high performance thin layer chromatographic method has been developed and validated for the quantification of Brexpiprazole in bulk drug and in pharmaceutical dosage form. The method employed HPTLC aluminum plates (pre-coated with silica gel 60 F254) as stationary phase while n-butanol was used as mobile phase. The Rf value of Brexpiprazole was observed to be 0.38. The densitometric analysis was carried out in absorbance mode at 215 nm. The linear regression analysis data for the calibration plots showed a good linear relationship for Brexpiprazole over a concentration range of 200-1,600 ng band-1. The limit of detection and limit of quantification for Brexpiprazole was found to be 66 and 200 ng band-1. To find out the possible degradation pathway, forced degradation studies were performed. The stock solutions of Brexpiprazole (1,000 μg mL-1) were subjected to acid and alkali hydrolysis, chemical oxidation, dry heat degradation and photo degradation. The drug was found to be susceptible to acid and alkali hydrolysis, chemical oxidation, photo degradation and dry heat. The degraded product peaks were well resolved from the pure drug peak with significant difference in their Rf values. Stressed samples were analyzed using developed HPTLC method. The proposed method was validated with respect to linearity, accuracy, precision and robustness. The method was successfully applied to the estimation of Brexpiprazole in marketed formulation and determination of content uniformity of tablet formulation. Statistical analysis showed that the method is repeatable, selective, and precise.
- Inhibition of Recombinant Human Acetylcholinesterase Activity by Antipsychotics. [News]
- PPharmacology 2019 May 08; 104(1-2):43-50
- CONCLUSIONS: Aripiprazole may cause EPS at clinical dosages by augmenting cholinergic effects via AChE inhibition, in addition to its suppressive effect on dopaminergic neurons.
- Medication-Induced Akathisia with Newly Approved Antipsychotics in Patients with a Severe Mental Illness: A Systematic Review and Meta-Analysis. [Review]
- CDCNS Drugs 2019; 33(6):549-566
- CONCLUSIONS: The use of a NAP raises the akathisia risk more than two-fold when compared with patients receiving placebo. Although distinctions between the different NAPs were not clear in placebo-controlled trials, the results of our meta-analyses and systematic review generally indicate that these differences more than likely reflect real differences, with iloperidone showing the most and cariprazine showing the least benign akathisia profile. Moreover, due to patient characteristics and methodological issues, incidence rates of akathisia with NAPs found in this meta-analysis may even be an underestimation of true incidence rates.
- A Long-Term, Open-Label Study to Evaluate the Safety and Tolerability of Brexpiprazole as Adjunctive Therapy in Adults With Major Depressive Disorder. [Journal Article]
- JCJ Clin Psychopharmacol 2019 May/Jun; 39(3):203-209
- CONCLUSIONS: Adjunctive treatment with open-label brexpiprazole 0.5 to 3 mg/d was generally well tolerated for up to 52 weeks in patients with MDD and was associated with continued improvement in efficacy measures and functional outcomes.
- In silico, in vitro and in vivo metabolite identification of brexpiprazole using ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry. [Journal Article]
- RCRapid Commun Mass Spectrom 2019 May 15; 33(11):1024-1035
- CONCLUSIONS: All the 16 metabolites were identified and characterized using UHPLC/QTOF-MS/MS. The study revealed that brexpiprazole is metabolized via hydroxylation, glucuronidation, S-oxidation, N-oxidation, dioxidation, oxidative deamination, N-dealkylation, etc.
- 14 Long-term Efficacy of Brexpiprazole in Patients with Schizophrenia with Clinically Relevant Levels of Negative Symptoms. [Journal Article]
- CSCNS Spectr 2019; 24(1):180
- CONCLUSIONS: This post-hoc analysis suggests that brexpiprazole has long-term effectiveness on negative symptoms and functioning in patients with schizophrenia and clinically relevant levels of negative symptoms.Funding Acknowledgements: The study was funded by Otsuka Pharmaceutical Development & Commercialization Inc. and H. Lundbeck A/S.
- Escalation of Gambling Associated With Aripiprazole: A Case Report and Literature Review. [Journal Article]
- JPJ Psychiatr Pract 2019; 25(2):139-145
- Impulse-control problems such as gambling, increased spending, hypersexuality, and compulsive eating are thought to be influenced by temperamental, genetic, and physiological risk factors. In additio…
Impulse-control problems such as gambling, increased spending, hypersexuality, and compulsive eating are thought to be influenced by temperamental, genetic, and physiological risk factors. In addition, dopamine receptor agonists have been implicated in some cases. It is postulated that aripiprazole may cause impulse-control problems because it can produce a hyperdopaminergic state in the mesolimbic pathway (reward system) through its predominant action on dopamine D3 receptors. We present the case of a patient with bipolar disorder and previous gambling behavior, in whom the gambling behavior escalated with the introduction of aripiprazole and its upward titration. The patient's gambling problems were alleviated with a decrease in aripiprazole dosage. Clinicians should be vigilant for possible gambling and other impulse-control behaviors in patients taking aripiprazole. Our literature review suggests cariprazine and brexpiprazole, which have mechanisms of action similar to that of aripiprazole, may also be associated with possible risks of impulse-control problems and pathologic gambling.
- A pilot study of brexpiprazole for bipolar depression. [Journal Article]
- JAJ Affect Disord 2019 Apr 15; 249:315-318
- CONCLUSIONS: A limitation to this study is the open-label design.To our knowledge, this is the first study to examine the effects of brexpiprazole on bipolar depression. We found a significant reduction in depressive symptoms and an increase in quality of life.
New Search Next
- Clinical Use of Dopamine Modulators as Third-Generation Antipsychotic Agents. [Journal Article]
- JPJ Psychosoc Nurs Ment Health Serv 2019 Feb 01; 57(2):7-11
- When dopamine was identified as a primary target for schizophrenia, the dopamine antagonists, now referred to as first-generation antipsychotics, were added to our pharmacopeia. In the 1990s, with th…
When dopamine was identified as a primary target for schizophrenia, the dopamine antagonists, now referred to as first-generation antipsychotics, were added to our pharmacopeia. In the 1990s, with the discovery of risperidone and clozapine, the mechanism of dopamine receptor antagonism was paired with serotonin receptor antagonism to give rise to second-generation antipsychotics. A decade later these mechanisms were further refined to selective dopamine receptors antagonism and serotonin receptors antagonism and agonism to create a modulation or stabilization of dopamine nerve firing in differential ways. This new wave may be referred to as the third generation. The current article reviews the pharmacodynamics and pharmacokinetics of these dopamine modulators. [Journal of Psychosocial Nursing and Mental Health Services, 57(2), 7-11.].