| 1 | J. Med. Chem. 2000 Dec 43: 4893-909 |
|---|---|
| PMID | 11123999 |
| Title | 2-氨基-3或6-氟烷烃的合成，SARS和药理表征[3.1.0]己烷-2,6-二羧酸衍生物是有效的，选择性和口服活性的II组II型分类型谷氨酸受体受体。 |
| 抽象的 | (+) 2-aminobicyclo [3.1.0] hexane-2 6-dicarboxyliccid (4, LY354740), a highly selective and orally active group II metabotropic glutamate receptor (mGluR) agonist, has increased interest in the study of group II mGluRs. Our interest focused on a conformationally constrained form of compound 4, because it appeared that the rigid form resulted in not only selectivity for group II mGluR but was orally active. Therefore, we introduced a fluorine atom to compound 4, based on the molecular size (close resemblance to hydrogen atom) and electronegativity (effects on the electron distribution in the molecule) of this atom and carbon-fluorine bond energy. Compound (+)-7 (MGS0008), the best compound among 3-fluoro derivatives 7-10, retained the agonist activity of compound 4 for mGluR2 and mGluR3 ((+)-7: EC(50) = 29.4 +/- 3.3 nM and 45.4 +/- 8.4 nM for mGluR2 and mGluR3, respectively; 4: EC(50) = 18.3 +/- 1.6 nM and 62.8 +/- 12 nM for mGluR2 and mGluR3, respectively) and increased the oral activity of compound 4 ((+)-7: ED(50) = 5.1 mg/kg and 0.26 mg/kg for phencyclidine (PCP)-induced hyperactivity and PCP-induced head-weaving behavior, respectively; 4: ED(50) = >100 mg/kg and 3.0 mg/kg for PCP-induced hyperactivity and PCP-induced head-weaving behavior, respectively). In addition, a compound [(3)H]-(+)-7 binding study using mGluR2 or 3 expressed in CHO cells was successful ((+)-7: K(i) = 47.7 +/- 17 nM and 65.9 +/- 7.1 nM for mGluR2 and mGluR3, respectively; 4: K(i) = 23.4 +/- 7.1 nM and 53.5 +/- 13 nM for mGluR2 and mGluR3, respectively). On the basis of a successful result of compound 7, we focused on the introduction of a fluorine atom on the C6 position of compound 4. (1R,2S,5R, 6R)-2-amino-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid ((-)-11) exhibited a high degree of agonist activity for group II mGluRs equal to that of compound 4 or 7 ((-)-11: K(i) = 16.6 +/- 5.6 and 80.9 +/- 31 nM for mGluR2 and mGluR3, respectively). Our interest shifted to modification on CH(2) at C4 position of compound 11, since replacement of the CH(2) group with either an oxygen atom or sulfur atom yielded compound 5 or 6, resulting in increased agonist activity. We selected a carbonyl group instead of CH(2) at the C4 position of compound 11. The carbonyl group might slightly change the relative conformation of three functional groups, the amino group and two carboxylic acids, which have important roles in mediating the interaction between group II mGluRs and their ligand, compared with the CH(2) group of 4, oxygen atom of 5, and sulfur atom of 6. (1R,2S,5S,6S)-2-Amino-6-fluoro-4-oxobicyclo[3.1. 0]hexane-2,6-dicarboxylic acid monohydrate ((+)-14, MGS0028) exhibited a remarkably high degree of agonist activity for mGluR2 (K(i) = 0.570 +/- 0.10 nM) and mGluR3 (K(i) = 2.07 +/- 0.40 nM) expressed in CHO cells but not mGluR4, 6, 7, 1a, or 5 expressed in CHO cells (K(i) = >100 000 nM). Furthermore, compound (+)-14 strongly inhibited phencyclidine (PCP)-induced head-weaving behavior (ED(50) = 0.090 microg/kg) and hyperactivity (ED(50) = 0.30 mg/kg) in rats. Thus, (+)-7 and (+)-14 are potent, selective, and orally active group II mGluR agonists and might be useful not only for exploring the functions of mGluRs but in the treatment ofschizophrenia。 |
| SCZ关键字 | 精神分裂症，精神分裂症 |
| 2 | Hum Psychopharmacol 2002 8月17日：305-7 |
| PMID | 12404676 |
| Title | 迟发性运动障碍和葡萄糖耐受性受损。 |
| 抽象的 | 作者研究了葡萄糖代谢受损在迟发性运动障碍的病理生理学中的作用schizophrenicpatients with and without persistent TD. Glucose tolerance and insulin levels were determined in 86 patients with persistent tardive dyskinesia and in 108 patients without tardive dyskinesia. Dyskinesias were assessed by the abnormal involuntary movement scale (AIMS) and extrapyramidal symptoms by the Simpson--Angus rating scale (SARS）。Fasting blood glucose levels were significantly lower while the first and second hour glucose levels did not reveal any differences in patients with tardive dyskinesia compared with those without tardive dyskinesia. Insulin levels did not differ in these two groups. Our cross-sectional epidemiological study does not suggest hyperglycemia to be a risk factor for tardive dyskinesia. However, prospective long-term studies with multiple assessment points are needed to clarify the role of glucose metabolism in the development of tardive dyskinesia. |
| SCZ关键字 | 精神分裂症，精神分裂症 |
| 3 | Schizophr. Res. 2003 Jan 59: 67-71 |
| PMID | 12413644 |
| Title | Clinical characteristics and associated factors in antipsychotic-induced akathisia of Asian patients with schizophrenia. |
| 抽象的 | 我们研究了Akathisia的患病率及其与许多社会人口统计学和临床因素的关系schizophrenia。 招募了6005名患者进行研究。使用Barnes Akathisia评级量表（BAR），异常非自愿运动量表（AIMS）和锥体外副作用（EPSE）评估了Akathisia（bars），通过Simpson-Angus评级量表（EPSE）评估（EPSE）（EPSE）（EPSE）（EPSE）（EPSE）（EPSE）（EPSE）（EPSE）（EPSE）（EPSE）（EPSE）（EPSE）（EPSE）（SARS）。 Only 35 (5%) patients were assessed to have akathisia. There was no gender or ethnic difference in the rates of akathisia. However, the majority of the patients (65%) were receiving an anticholinergic agent at the time of the study. 我们关于TD和EPSE之间重叠的发现支持了以下建议：这些运动障碍可能存在共同的脆弱性。在我们的亚洲患者中发现降低速率较低的发现表明族裔间脆弱性的脆弱性差异。但是，将我们的结果与其他国家报告的比率进行比较可能会受到研究之间的诊断和方法学差异的阻碍。 |
| SCZ关键字 | 精神分裂症，精神分裂症 |
| 4 | Isr J Psychiatry Relat Sci 2005 -1 42: 258-62 |
| PMID | 16618059 |
| Title | Psychiatric inpatients' reactions to the SARS epidemic: an Israeli survey. |
| 抽象的 | 潜在传播的威胁SARS流行病给许多未受影响国家的人带来了重大压力。在这项研究中，我们调查了是否SARSthreat affected the subjective mood and behavior of Israeli patients withschizophreniaand compared their reactions with those noted in their clinical staff. Subjects were evaluated with a specially designed questionnaire and a modified form of the Spielberger Scale for State Anxiety. As compared to staff, patients had higher scores on the Modified Spielberger State Anxiety Scale. However, many responses (e.g., dysphoria) to theSARSthreat did not differ from staff. Patients felt more protected by the authorities and some perceived the epidemic in a psychotic manner. 看来，患者试图通过生活在“自闭症泡沫”（外部威胁无法进入）或否认这些压力源的意义并过分强调医疗当局保护它们的力量中来减少外部压力源的影响。另一方面，一些患者还在心理上解释了这些压力源。 |
| SCZ关键字 | 精神分裂症，精神分裂症 |
| 5 | 精神病学Res 2006年9月144日：57-63 |
| PMID | 16904189 |
| Title | 精神分裂症患者抑郁症评估量表的诊断有效性。 |
| 抽象的 | 这项研究的目的是检查四个常用评估量表的诊断有效性schizophrenia。该研究人群包括84名符合DSM-IV标准的住院患者schizophrenia。Depression in the study subjects was defined by the DSM-IV criteria for major depressive episode. The Positive and Negative Syndrome Scale (PANSS) and the Simpson-Angus Rating Scale (SARS）用于区分抑郁症与腹膜外症状相关的阴性和抑郁现象schizophrenia。评估了以下四个抑郁量表的诊断有效性，作为抑郁症的措施schizophrenia：卡尔加里抑郁量表schizophrenia(CDSS), the Beck Depression Inventory (BDI), the Hamilton Rating Scale for Depression (HAM-D), and the depression subscale of the PANSS (PANSS-D). Of 84 patients withschizophrenia，32被诊断为合并性抑郁症。CDSS，HAM-D，PANSS-D和BDI的接收器工作特性（ROC）曲线下的区域分别为0.94、0.89、0.90和0.81。CDSS的ROC曲线下的面积明显大于BDI的面积，并且比HAM-D和PANSS-D的面积往往比HAM-D和PANSS-D更有利。我们的研究表明，CDS可以为患者的患者提供最佳评估schizophrenia。 |
| SCZ关键字 | 精神分裂症，精神分裂症 |
| 6 | Bioorg. Med. Chem. Lett. 2008 Jun 18: 3386-91 |
| PMID | 18455394 |
| Title | 发现融合的吡咯羧酸作为新颖的有效D-氨基酸氧化酶（DAO）抑制剂。 |
| 抽象的 | The 'NMDA hypofunction hypothesis ofschizophrenia可以通过多种方式进行测试。刀是在zyme primarily responsible for the metabolism of d-serine, a co-agonist for the NMDA receptor. We identified novel DAO inhibitors, in particular, acid 1, which demonstrated moderate potency for DAO in vitro and ex vivo, and raised plasma d-serine levels after dosing ip to rats. In parallel, analogues were prepared to survey theSARS1。 |
| SCZ关键字 | 精神分裂症，精神分裂症 |
| 7 | Zh Nevrol Psikhiatr Im S S Korsakova 2008 -1 108: 28-33 |
| PMID | 18577931 |
| Title | [使用硝苯地平作为经典神经摄影的锥体外副作用的校正者]。 |
| 抽象的 | The aim of the article was to study efficacy and safety of nifedipine in the correction of extrapyramidal side-effects emerged during conventional neuroleptics therapy. Fifty-one patients diagnosed with paranoidschizophreniareceived haloperidol in combination with nifedipine (25 patients) or haloperidol only (26 patients) during 26 weeks. Dynamics of psychopathological symptoms and extrapyramidal disorders were measured with PANSS, CGI, BARS,SARSand AIMS. Patients receiving haloperidol in combination with nifedipine had the lower AIMS scores indicating appearances of dyskinesia and less marked (on the trend to statistical significance)SARSscores measuring parkinsonian symptoms as compared to patients receiving monotherapy with haloperidol. The administration of nifedipine in combination with haloperidol did not reduce the therapeutic efficacy of the latter and did not lead to the increase of side-effects. The data obtained suggest that nifedipine may be used as a perspective corrector of extrapyramidal disorders caused by classical neuroleptics. |
| SCZ关键字 | 精神分裂症，精神分裂症 |
| 8 | Parkinsonism Relat. Disord. 2009 Nov 15: 655-9 |
| PMID | 19346155 |
| Title | 菲律宾精神分裂症患者的当前患病率和与迟发性运动障碍有关的因素。 |
| 抽象的 | To determine the prevalence of and the factors associated with tardive dyskinesia (TD) among Filipino patients withschizophreniaadmitted at the National Center for Mental Health. 横断面研究。 A total of 227 inpatients fulfilling the DSM-IV TR criteria forschizophrenia参加了研究。获得了包括年龄，疾病持续时间和药物摄入的人口统计数据。异常非自愿运动量表（AIMS）和Simpson Angus评级量表（SARS）对所有患者进行。计算了与不同变量相关的TD的几率。还使用卡方检验评估了研究变量与TD发展之间的关联。 我们的队列的平均年龄为40岁（范围：19-73岁），平均疾病持续时间为6年，每天的毒性剂量为700 mg，氯丙胺等效剂量为700 mg，并且至少具有一生5年。TD的患病率为20.3％（227例患者中有46例）。53％的患者具有明显的锥体腹腹膜牙齿特征（SARS>或= 3）。在女性和年龄段的年龄段中，TD更多。与TD相关的其他因素是：那些疾病持续时间更长的患者和那些累积累积暴露于神经饱和药物的患者。关于II型糖尿病的存在，与抗胆碱能药物的使用，与药物滥用史以及电击疗法的史相关。 Despite the predominant use of first-generation antipsychotic agents, the prevalence of TD among Filipinoschizophrenic患者与在亚洲人中报道的相似，但低于我们西方同行报道的患者。结果可能会受到方法论，种族和遗传决定因素的差异的影响。 |
| SCZ关键字 | 精神分裂症，精神分裂症 |
| 9 | Parkinsonism Relat. Disord. 2009 Nov 15: 655-9 |
| PMID | 19346155 |
| Title | 菲律宾精神分裂症患者的当前患病率和与迟发性运动障碍有关的因素。 |
| 抽象的 | To determine the prevalence of and the factors associated with tardive dyskinesia (TD) among Filipino patients withschizophreniaadmitted at the National Center for Mental Health. 横断面研究。 A total of 227 inpatients fulfilling the DSM-IV TR criteria forschizophrenia参加了研究。获得了包括年龄，疾病持续时间和药物摄入的人口统计数据。异常非自愿运动量表（AIMS）和Simpson Angus评级量表（SARS）对所有患者进行。计算了与不同变量相关的TD的几率。还使用卡方检验评估了研究变量与TD发展之间的关联。 我们的队列的平均年龄为40岁（范围：19-73岁），平均疾病持续时间为6年，每天的毒性剂量为700 mg，氯丙胺等效剂量为700 mg，并且至少具有一生5年。TD的患病率为20.3％（227例患者中有46例）。53％的患者具有明显的锥体腹腹膜牙齿特征（SARS>或= 3）。在女性和年龄段的年龄段中，TD更多。与TD相关的其他因素是：那些疾病持续时间更长的患者和那些累积累积暴露于神经饱和药物的患者。关于II型糖尿病的存在，与抗胆碱能药物的使用，与药物滥用史以及电击疗法的史相关。 Despite the predominant use of first-generation antipsychotic agents, the prevalence of TD among Filipinoschizophrenic患者与在亚洲人中报道的相似，但低于我们西方同行报道的患者。结果可能会受到方法论，种族和遗传决定因素的差异的影响。 |
| SCZ关键字 | 精神分裂症，精神分裂症 |
| 10 | BMC精神病学2014年-1 14：166 |
| PMID | 24903304 |
| Title | Severity of psychotic episodes in predicting concurrent depressive and anxiety features in acute phase schizophrenia. |
| 抽象的 | Considering that depressive and anxiety symptoms are common inschizophrenia，这项研究调查了急性阶段精神病发作的严重程度schizophrenia队列可以预测并发抑郁和焦虑特征。 五十一名最近住院的患者患有急性期schizophreniaparticipated prospectively in a cross-sectional study. The severity of the psychotic episode, the depressive features and the anxiety features were measured by the Structured Clinical Interview for Positive and Negative Syndrome Scale (SCI-PANSS), the Calgary Depression Scale forschizophrenia（CDSS），汉密尔顿焦虑评分量表（HAM-A）和Stadenschizophrenia焦虑评分量表（S-SARS）。调整了总科幻分数，以适当排除其中包含的抑郁症或焦虑症。为了检查Akathisia作为潜在的混杂因素，还应用了Barnes Akathisia量表。使用线性回归检查了关系，并在科幻镜头上的较低分数和更高分数之间进行了配对的t检验。 A higher adjusted total SCI-PANSS-score predicted statistically significantly higher scores for depressive features on the CDSS (p < 0.0001) and for anxiety features on the HAM-A (p = 0.05) and the S-SARS(p < 0.0001). The group that scored more or equal to the median (=99) of the adjusted total SCI-PANSS, scored significantly higher (p < 0.0001) on the CDSS, the HAM-A and the S-SARS比在下面得分的小组得分。Akathisia与两种焦虑措施的测量均明显不同（P <0.0001）。 该研究表明，急性阶段精神病发作的严重程度schizophrenia分别预测并发抑郁和焦虑特征的严重程度。 |
| SCZ关键字 | 精神分裂症，精神分裂症 |