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Brexpiprazole for the treatment of schizophrenia

Yee A

Expert Rev Neurother, 2016;16(2):109-22.
PMID: 26650624 DOI: 10.1586/14737175.2016.1129901

Brexpiprazole (OPC-34712) is a novel serotonin-dopamine activity modulator, which has recently been approved by the U.S Food and Drug Administration for the treatment of schizophrenia. The aim of this paper is to systematically synthesize all data of the efficacy, safety and tolerability of Brexpiprazole in treating schizophrenia. The terms 'Brexpiprazole', 'OPC-34712' and 'schizophrenia' were searched. A total of 12 clinical trials with 7 available data records were found. The pooled effect size of Brexpiprazole 1 mg, 2 mg and 4 mg were all superior to placebo in terms of the change from baseline in positive and negative syndrome scale (PANSS) total score at week 6 (weighted mean difference = -3.74, p = 0.044; weighted mean difference = -5.76, p

Matched MeSH terms: Serotonin Agents/therapeutic use*
Acute serotonergic treatment changes the relation between anxiety and HPA-axis functioning and periaqueductal gray activation

Hestermann D, Temel Y, Blokland A, Lim LW

Behav Brain Res, 2014 Oct 15;273:155-65.
PMID: 25043730 DOI: 10.1016/j.bbr.2014.07.003

Serotonergic (5-HT) drugs are widely used in the clinical management of mood and anxiety disorders. However, it is reported that acute 5-HT treatment elicits anxiogenic-like behavior. Interestingly, the periaqueductal gray (PAG), a midbrain structure which regulates anxiety behavior - has robust 5-HT fibers and reciprocal connections with the hypothalamic-pituitary-adrenal (HPA) axis. Although the HPA axis and the 5-HT system are well investigated, the relationship between the stress hormones induced by 5-HT drug treatment and the PAG neural correlates of the behavior remain largely unknown. In this study, the effects of acute and chronic treatments with buspirone (BUSP) and escitalopram (ESCIT) on anxiety-related behaviors were tested in an open-field (OF). The treatment effects on PAG c-Fos immunoreactivity (c-Fos-ir) and corticosterone (CORT) concentration were measured in order to determine the neural-endocrine correlates of anxiety-related behaviors and drug treatments. Our results demonstrate that acute BUSP and ESCIT treatments induced anxiogenic behaviors with elevation of CORT compared to the baseline. A decrease of c-Fos-ir was found in the dorsomedial PAG region of both the treatment groups. Correlation analysis showed that the CORT were not associated with the OF anxiogenic behavior and PAG c-Fos-ir. No significant differences were found in behaviors and CORT after chronic treatment. In conclusion, acute BUSP and ESCIT treatments elicited anxiogenic response with activation of the HPA axis and reduction of c-Fos-ir in the dorsomedial PAG. Although no correlation was found between the stress hormone and the PAG c-Fos-ir, this does not imply the lack of cause-and-effect relationship between neuroendocrine effects and PAG function in anxiety responses. These correlation studies suggest that the regulation of 5-HT system was probably disrupted by acute 5-HT treatment.

Matched MeSH terms: Serotonin Agents/administration & dosage*
Anxiolytic- and antidepressant-like activities of a methanolic extract of Morinda citrifolia Linn. (noni) fruit in mice: Involvement of benzodiazepine-GABAAergic, serotonergic and adrenergic systems

Narasingam M, Vijeepallam K, Mohamed Z, Pandy V

Biomed Pharmacother, 2017 Dec;96:944-952.
PMID: 29217165 DOI: 10.1016/j.biopha.2017.11.148

This study presents anxiolytic- and antidepressant-like effects of a methanolic extract of Morinda citrifolia Linn. (noni) fruit (MMC) in well-established mouse models of anxiety and depression. The administration of MMC (1 g/kg, p.o.) and diazepam (1 mg/kg, i.p.) significantly attenuated anxiety-like behaviour in mice by increasing the percentage of time spent and number of entries in the open arms in the elevated plus maze (EPM), and significantly enhanced the exploration in the light box in the light/dark test (LDT). The pre-treatment with flumazenil (6 mg/kg, i.p.) or bicuculline (3 mg/kg, i.p.) or WAY 100635 (1 mg/kg, i.p.) antagonized the anxiolytic-like effect elicited by MMC (1 g/kg, p.o.). These results suggest the possible involvement of benzodiazepine-GABAAergic and serotonergic mechanisms in the anxiolytic-like effect of noni fruit. Meanwhile, in the antidepressant study, the administration of MMC (0.5 and 0.75 g/kg, p.o.) and desipramine (30 mg/kg, i.p.) significantly reduced the duration of immobility in the tail suspension test (TST). Furthermore, pre-treatment of mice with 4-chloro-DL-phenylalanine methyl ester hydrochloride (PCPA; 100 mg/kg, i.p., an inhibitor of serotonin synthesis) for four consecutive days or a single dose of WAY 100635 (1 mg/kg, i.p., 5HT1A receptor antagonist) or α-methyl-DL-tyrosine (AMPT; 100 mg/kg, i.p., an inhibitor of noradrenaline synthesis) significantly reversed the anti-immobility effect of MMC (0.5 g/kg, p.o.) in TST by indicating the specific involvement of the serotonergic and noradrenergic systems in the antidepressant-like effect of noni fruit. Taken together, these findings suggest that MMC has both anxiolytic- and antidepressant-like activities to be resorted as a valuable alternative therapy for comorbid anxiety and depressive conditions.

Matched MeSH terms: Serotonin Agents/pharmacology*
Fulltext Metabolomics analysis of herb-partitioned moxibustion treatment on rats with diarrhea-predominant irritable bowel syndrome

Lin X, Liu X, Xu J, Cheng KK, Cao J, Liu T, et al.

Chin Med, 2019;14:18.
PMID: 31080495 DOI: 10.1186/s13020-019-0240-2

Background: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder, which is commonly treated with antidiarrhoeal, antispasmodics, serotonergic agents or laxative agents. These treatments provide relief for IBS symptoms but may also lead to undesired side effects. Previously, herb-partitioned moxibustion (HPM) treatment has been demonstrated to be effective in ameliorating symptoms of IBS. However, the underlying mechanism of this beneficial treatment is yet to be established. The aim of the current study was to systematically assess the metabolic alterations in response to diarrhea-predominant IBS (IBS-D) and therapeutic effect of HPM.
Methods: Proton nuclear magnetic resonance spectroscopy (1H NMR)-based metabolomics approach was used to investigate fecal and serum metabolome of rat model of IBS-D with and without HPM treatment.
Results: The current results showed that IBS-induced metabolic alterations in fecal and serum sample include higher level of threonine and UDP-glucose together with lower levels of aspartate, ornithine, leucine, isoleucine, proline, 2-hydroxy butyrate, valine, lactate, ethanol, arginine, 2-oxoisovalerate and bile acids. These altered metabolites potentially involve in impaired gut secretory immune system and intestinal inflammation, malabsorption of nutrients, and disordered metabolism of bile acids. Notably, the HPM treatment was found able to normalize the Bristol stool forms scale scores, fecal water content, plasma endotoxin level, and a number of IBS-induced metabolic changes.
Conclusions: These findings may provide useful insight into the molecular basis of IBS and mechanism of the HPM intervention.

Matched MeSH terms: Serotonin Agents