Publications by authors named "Koji Shinkai"

In the present study, we investigated the effects of risperidone treatment for 4 weeks on plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) and brain-derived neurotrophic factor (BDNF) in 89 schizophrenic patients. We also compared the plasma levels of BDNF and MHPG between the schizophrenic group and 103 sex-and age-matched normal controls. In addition, we investigated the effects of two SNPs of the noradrenaline transporter (NAT) gene on plasma levels of MHPG, BDNF, and clinical improvement.

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Milnacipran is a serotonin noradrenaline reuptake inhibitor (SNRI) and is used clinically as an antidepressant. We report here the effect of milnacipran on catecholamine synthesis in cultured bovine adrenal medullary cells. Incubation of adrenal medullary cells with milnacipran (300 ng/ml, 1,065 nM) for 20 min resulted in a significant increase in 14C-catecholamine synthesis from [14C]tyrosine, but not from [14C]DOPA, whereas the selective serotonin reuptake inhibitors (SSRIs), paroxetine (300 ng/ml, 800 nM) and fluvoxamine (300 ng/ml, 691 nM), had little effect.

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The authors report on the successful treatment of obsessive-compulsive disorder (OCD) in three patients with the addition of risperidone to ongoing fluvoxamine treatment. Plasma homovanillic acid (HVA), but not 3-methoxy-4-hydroxyphenylglycol (MHPG) levels decreased after risperidone administration, and plasma levels of fluvoxamine did not change. In addition, serum brain-derived neurotrophic factor (BDNF) levels were not altered after the recovery from obsessive-compulsive symptoms, indicating that serum BDNF levels might not predict the patient's response to risperidone treatment.

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In the preset study, the authors investigated that effects of the antipsychotic drug risperidone on psychotic depression and examined the mechanism of risperidone to ameliorate psychotic depression. Fifteen patients met the DSM-IV criteria for major depressive disorder with psychotic features and the remaining five patients met those for bipolar I disorder (most recent episode depressed) with psychotic features (M/F: 8/12, age: 54+/-18). All patients were evaluated regarding their clinical improvement using the Hamilton Rating Scale for Depression (Ham-D), and Positive and Negative Syndrome Scale (PANSS).

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Background: Previously, it was demonstrated that the inhibitory effects of atypical antipsychotic drugs such as clozapine and risperidone on noradrenaline transporter (NAT) might in part be associated with their clinical profile. The present study examined the effects of zotepine on NAT in the cells and compared them with those of olanzapine.

Materials And Methods: Adrenal medullary cells were isolated by a method of collagenase digestion of slices of fresh bovine adrenal medulla and the cells were plated at a density of 4 x 10(6) cells.

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The antidepressants milnacipran and paroxetine are used clinically worldwide. In the present study, we report here the effects of treatment with milnacipran and paroxetine on the functional activity, binding sites, and mRNA of the norepinephrine (NE) transporter (NET) in cultured bovine adrenal medullary cells. In acute treatment with antidepressants for 20 min, both milnacipran and paroxetine competitively inhibited NET function in cultured adrenal medullary cells.

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An open-label study was performed to investigate the clinical efficacy and mechanisms of risperidone liquid in ameliorating positive symptoms in the acute phase of schizophrenia. Eighty-eight patients (M/F: 50/38; age: 18-74 years;, mean +/- SD =32 +/- 16 years) meeting DSM-IV criteria for schizophrenia and treated with risperidone liquid (14 patients also used lorazepam) were evaluated with regard to their clinical improvement and extrapyramidal side effects using the positive and negative syndrome scale (PANSS) and the Simpson and Angus scale (SAS), while plasma concentrations of HVA and MHPG were analysed by HPLC-ECD before and 4 weeks after risperidone liquid administration. Patients showing a 50% or greater improvement in PANSS scores were defined as responders.

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In the present study, we examined the relationships between plasma concentrations of risperidone and clinical responses, extrapyramidal symptoms, plasma levels of cotinine and caffeine, or cytochrome (cyp)2D6 genotypes. In addition, we also investigated the relationships between plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) or homovanillic (HVA) acid and clinical responses to risperidone. One hundred and 36 patients (male/female: 58/78, age 37+/-13 years) who met DSM-IV criteria for schizophrenia, schizoaffective disorder, delusional disorder and brief psychotic disorder, and who were being treated with risperidone alone, were evaluated regarding their clinical improvement and extrapyramidal symptoms using the Positive and Negative Syndrome Scale (PANSS) and Simpson and Angus (SAS), respectively, and plasma levels of cotinine, caffeine, MHPG and HVA were analysed by high-performance liquid chromatography.

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Pimobendan, a Ca(2+) sensitizer, is used clinically in the treatment of chronic heart failure. Although chronic heart failure is associated with activation of the sympathetic nervous system, it remains unknown whether pimobendan affects the function of sympathetic neurons and the adrenal medulla. Here, we report the inhibitory effects of pimobendan on catecholamine secretion and synthesis in cultured bovine adrenal medullary cells.

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Plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) may provide valuable information regarding central noradrenergic activity. In this article, we mainly reviewed about the associations between plasma MHPG levels and responses to antidepressant treatment. There exists heterogeneity of depression with regards to plasma levels of MHPG; in other words, depressed patients might be dichotomized into one group characterized by anxiety and/or perceptions of powerlessness with high plasma MHPG levels and another group characterized by psychomotor retardation with low plasma MHPG levels.

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The purpose of this study was to investigate the effects of milnacipran and paroxetine on plasma levels of catecholamine metabolites, and we attempted to elucidate the differences between the mechanisms of these drugs in catecholaminergic neurons. In depressed patients, we investigated the relationships among pretreatment levels of catecholamine metabolites, the changes in plasma catecholamine metabolite levels before and after administration of milnacipran or paroxetine, and clinical response to these drugs. Responders to milnacipran showed lower pretreatment levels of plasma 3-methoxy-4-hydroxyphenylglycol (pMHPG) than did nonresponders to milnacipran; there was also a positive correlation between changes in pMHPG levels and percent improvement of the score on the 17-item Hamilton Rating Scale for Depression (HRSD).

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We investigated the association between selective serotonin reuptake inhibitors (SSRIs; paroxetine or fluvoxamine) and nausea with regard to plasma 5-hydroxyindoleacetic acid (p5-HIAA) levels. Forty-eight patients meeting the DSM-IV criteria for major depressive disorder and treated with paroxetine or fluvoxamine participated in this study. p5-HIAA levels after SSRI administration were significantly higher in the nausea group than those in the nonnausea group (nausea group: 8.

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We have previously reported that risperidone might improve negative symptoms in schizophrenia by influencing noradrenergic neurons. In the present study, we focused on the clinical efficacy and mechanisms of risperidone towards positive symptoms in the acute phase of schizophrenia. Thirty-four patients meeting DSM-IV criteria for schizophrenia and treated with risperidone alone were evaluated regarding their clinical improvement using the Positive and Negative Syndrome Scale (PANSS) before and 2 weeks after risperidone administration, and blood samples were also drawn at the same times.

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