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갠지하시모토 대한정신약물학회 2006 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.4 No.1
Multiple lines of evidence suggest that an abnormality of glutamatergic neurotransmission via N-methyl-D-aspartate (NMDA) receptors might be implicated in the pathophysiology of schizophrenia. Considering the NMDA receptor hypofunction hypothesis for schizophrenia, increasing NMDA receptor function by pharmacological manipulation could potentially be a new strategy for the management of schizophrenia. Currently, the NMDA receptor glycine modulatory site is the most attractive therapeutic target for improving cognition and reducing negative symptoms in schizophrenia. It has been shown that glycine transporter-1 (GlyT-1) inhibitors and D-serine (an endogenous co-agonist at glycine modulatory site) could be potential drugs for treating schizophrenia, since the permeability of glycine into the brain is poor. In this article, the author reviews the NMDA receptor hypofunction hypothesis for schizophrenia, and the author discusses potential therapeutic drugs, including glycine transporter-1 (GlyT-1) inhibitors and D-serine.
갠지하시모토,Yuko Fujita,Mao Horio,Hiroko Hagiwara,Yuko Tanibuchi,Masaomi Iyo 대한정신약물학회 2010 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.8 No.2
This study was undertaken to examine the effects of cilostazol, a selective inhibitor of type III phosphodiesterase (PDE), on hyperlocomotion and prepulse inhibition (PPI) deficits in mice after a single administration of the N-methyl-D-aspartate (NMDA)receptor antagonist dizocilpine. A single oral administration of cilostazol (0.1 and 0.3 mg/kg) significantly attenuated hyperlocomotion and PPI deficits in mice after the administration of dizocilpine (0.1 mg/kg, subcutaneously). This study suggests that cilostazol may have antipsychotic activity in animal models of schizophrenia. Therefore, cilostazol may be a potential therapeutic drug for schizophrenia, given that cilostazol has been safely used throughout the world.
Effects of Cilostazol on Cognitive Deficits in Mice after Repeated Administration of Phencyclidine
갠지하시모토,Yuko Fujita,Tamaki Ishima,Mao Horio,Hiroko Hagiwara,Yuko Tanibuchi,Masaomi Iyo 대한정신약물학회 2010 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.8 No.1
Objective : To examine the effects of cilostazol, a selective inhibitor of type III phosphodiesterase (PDE), on cognitive deficits in mice after repeated administration of the N-methyl-D-aspartate (NMDA) receptor antagonist phencyclidine (PCP). Methods:Saline (10 ml/kg/day) or PCP (10 mg/kg/day) were administered subcutaneously to mice for 10 days (once daily on days 1−5 and 8−12). Three days (day 15) after the final administration of saline or PCP, vehicle (0.5% carboxymethylcellulose)or cilostazol (0.3, 3, 10 or 30 mg/kg/day) were administered orally for 14 consecutive days (once daily on days 15−28). The novel object recognition test (NORT) was performed 24 hours (day 29) after the final administration. Results:In the NORT, PCP -induced cognitive deficits in mice were improved significantly by subsequent sub-chronic (14 days)administration of cilostazol (3, 10 or 30 mg/kg/day), but not by the lowest dose of cilostazol (0.3 mg/kg/day). Conclusion:This study suggests that cilostazol ameliorates PCP-induced cognitive deficits in mice. Therefore, it is likely that cilostazol has therapeutic potential for cognitive deficits in schizophrenia.
Yakup Albayrak,갠지하시모토 대한신경정신의학회 2013 PSYCHIATRY INVESTIGATION Vol.10 No.4
Fluvoxamine is a selective serotonin reuptake inhibitor that is approved for psychiatric disorders such as major depressive episodes and obsessive-compulsive disorder. Beside inhibition of serotonin reuptake, fluvoxamine is also a potent agonist of endoplasmic reticulum (ER) protein sigma-1 receptors, which play a role in the pathophysiology of a number of psychiatric and neurodegenerative disorders. This report presents beneficial effects of sigma-1 agonist fluvoxamine on hyperkinetic movement disorders such as tardive dyskinesia and tardive akathisia. Fluvoxamine might be a novel treatmet approach in the treatment of hyperkinetic movement disorders.
Yumi Shirai,Yuko Fujita,갠지하시모토 대한정신약물학회 2012 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.10 No.2
Objective: Accumulating evidence suggests that oxidative stress plays a role in the pathophysiology of schizophrenia and that the potent antioxidants may be potential therapeutic drugs for schizophrenia. This study was undertaken to examine the effects of the potent antioxidant sulforaphane (SFN), found in cruciferous vegetables, on behavioral abnormalities (e.g., hyperlocomotion and prepulse inhibition [PPI] deficits) in mice after a single administration of the N-methyl-D-aspartate (NMDA)-receptor antagonist phencyclidine (PCP). Methods: Effects of SFN (3, 10, and 30 mg/kg, intraperitoneally [i.p.]) on hyperlocomotion and PPI deficits in the adult male ddY mice after administration of PCP (3.0 mg/kg, subcutaneously [s.c.]) were examined. Results:Administration of SFN (30 mg/kg, intraperitoneally [i.p.]), but not low doses (3 and 10 mg/kg, i.p.), significantly attenuated hyperlocomotion in mice after PCP administration (3.0 mg/kg, subcutaneously [s.c.]). Furthermore, administration of SFN (3, 10, and 30 mg/kg, i.p.) attenuated the PPI deficits in mice after PCP administration (3.0 mg/kg, s.c.) in a dose-dependent manner. Conclusion: These results suggest that SFN has antipsychotic activity in an animal model of schizophrenia. Therefore, it is likely that SFN may be a potential therapeutic drug for schizophrenia.
Su-Xia Li,갠지하시모토,Ji-chun Zhang,Jin Wu 대한정신약물학회 2014 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.12 No.2
Objective: Pediatric depression is associated with significant functional impairment at school and at work. Recently, we reportedon depression-like behavior in juvenile mice neonatally exposed to dexamethasone (DEX) as a potential animal model for pediatricdepression. The N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has promoted rapid and long-lasting antidepressanteffects in patients with treatment-resistant major depression. This study was conducted to examine whether ketaminehad antidepressant effects in juvenile mice after neonatal DEX exposure. Methods: A single dose (10 mg/kg) of ketamine or vehicle was injected into juvenile mice at days 29-32 after neonatal DEX(or saline) exposure (days 1-3). The sucrose preference test, tail suspension test, and forced swimming test were performed24, 40, and 46 hours, respectively, after injection of ketamine. Results: Ketamine (10 mg/kg) significantly improved depression-like behavior in DEX-treated juvenile mice. Conclusion: This finding suggests that ketamine confers antidepressant effects in an animal model of pediatric depression
Akira Kishimoto,Yurie Goto,갠지하시모토 대한정신약물학회 2014 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.12 No.3
Post-traumatic stress disorder (PTSD) is a pathological response to trauma characterized by frequent recollections, recurrentnightmares, and flashbacks of the traumatic event(s). To date, the precise mechanisms underlying the development of PTSDremain unknown. Several studies have suggested that antiepileptic drugs, such as gabapentin and lamotrigine, may be effectivein the treatment of PTSD symptoms. We report on a 15-year-old Japanese female junior high school student who developedPTSD symptoms following repeated teasing from male classmates. Additionally, we underscore the beneficial effects of treatmentwith gabapentin and lamotrigine on flashbacks and nightmares. This patient developed PTSD symptoms after repeated teasingfrom male classmates at school. Her flashbacks and nightmares were treated with a combination of gabapentin and lamotrigine. After recovery, treatment with lamotrigine alone controlled her symptoms. Our observations suggest that a process of sensitizationmay be involved in the development of PTSD symptoms. Additionally, gabapentin and/or lamotrigine were effective in the treatmentof flashbacks and nightmares in this patient. Thus, doctors should consider using these anti-epileptic drugs as an alternativeapproach to treating PTSD symptoms.
Shigenori Tadokoro,Naho Nonomura,Nobuhisa Kanahara,갠지하시모토,Masaomi Iyo 대한정신약물학회 2017 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.15 No.1
Dopamine supersensitivity psychosis (DSP) is a type of acute exacerbation of recurrent psychosis caused by long-term treatment with antipsychotics in schizophrenic patients. Although DSP is exceedingly troublesome for clinicians, effective treatment has not yet been established. Based on clinical research and our animal study, we hypothesize that aripiprazole, an atypical antipsychotic, may reduce the exacerbation of recurrent psychotic episodes. We report the case of a 46-year-old female who suffered from schizophrenia with DSP. In this case, sustained treatment with a high dose of aripiprazole gradually reduced the severity of her recurrent psychotic episodes. In conclusion, sustained treatment with aripiprazole may reduce the exacerbation of recurrent psychotic episodes in schizophrenic patients with DSP, and may be an effective treatment of DSP.
Min Ma,Qian Ren,Ji-chun Zhang,갠지하시모토 대한정신약물학회 2014 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.12 No.1
Objective: Accumulating evidence suggests that inflammation plays a role in the pathophysiology of major depression. The adenosinetriphosphate (ATP)-sensitive P2X7 receptor (P2X7R) plays a crucial role in microglial activation caused by inflammation. The dye brilliant blue G (BBG) is a P2X7R antagonist. This study examined whether BBG shows antidepressant effects in aninflammation-induced model of depression. Methods: We examined the effects of BBG (12.5, 25, or 50 mg/kg) on serum tumor necrosis factor-α (TNF-α) levels afteradministering the bacterial endotoxin lipopolysaccharide (LPS; 0.5 mg/kg) and the effects of BBG (50 mg/kg) on depression-likebehavior in the tail-suspension test (TST) and forced swimming test (FST). Results: Pretreatment with BBG (12.5, 25, or 50 mg/kg) significantly blocked the increase in serum TNF-α levels after a singledose of LPS (0.5 mg/kg). Furthermore, BBG (50 mg/kg) significantly attenuated the increase in immobility time in the TST andFST after LPS (0.5 mg/kg) administration. Conclusion: The results suggest that BBG has anti-inflammatory and antidepressant effects in mice after LPS administration. Therefore, P2X7R antagonists are potential therapeutic drugs for inflammation-related major depression.
Mei Han,Ji-chun Zhang,갠지하시모토 대한정신약물학회 2017 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.15 No.1
Objective: Prenatal infection is implicated in the etiology of schizophrenia. The objective of this paper is to study the role of complement protein C1q in the psychosis of adult offspring after maternal immune activation (MIA). In addition, effect of 7,8-dihydroxyflavone (7,8-DHF: a tropomyosin receptor kinase B [TrkB] agonist) was also examined. Methods: Western blot analysis of C1q in the brain regions from adult offspring after prenatal poly(I:C) (5.0 mg/kg/day from E12 to E17) exposure was performed. 7,8-DHF or vehicle was given from 4 to 8-weeks old. Results: Expression of C1q in the prefrontal cortex (PFC) of adult offspring from poly(I:C)-treated pregnant mice was significantly higher than that of control group. Early treatment with 7,8-DHF during juvenile and adolescent stages could prevent an increase of C1q in the PFC of adult offspring after MIA. Conclusion: Therefore, it is likely that increased C1q expression in the frontal cortex may play a role in the behavioral abnormalities of adult offspring after MIA. Furthermore, supplementation with a TrkB agonist such as 7,8-DHF during the prodromal stage may have prophylactic effects on the behavioral abnormalities after MIA.