| 1 | Neuropsychopharmacology 2007 Mar 32: 658-64 |
|---|---|
| PMID | 16738540 |
| Title | 选择性5-羟色胺再摄取抑制剂，氟西汀和帕罗西汀，减轻了甲基苯丙胺诱导的已建立行为敏化的表达。 |
| 抽象的 | 获得一个洞察一个新发展pharmacotherapy that prevents the treatment-resistant relapse of psychostimulant-induced psychosis andschizophrenia，我们在小鼠中研究了选择性5-羟色胺再摄取抑制剂（SSRI），氟西汀（FLX）和帕罗西汀（PRX), on the established sensitization induced by methamphetamine (MAP), a model of the relapse of these psychoses, because the modifications of the brain serotonergic transmission have been reported to antagonize the sensitization phenomenon. In agreement with previous reports, repeated MAP treatment (1.0 mg/kg a day, subcutaneously (s.c.)) for 10 days induced a long-lasting enhancement of the increasing effects of a challenge dose of MAP (0.24 mg/kg, s.c.) on motor activity on day 12 or 29 of withdrawal. The daily injection of FLX (10 mg/kg, s.c.) orPRX（8 mg/kg，s.c。）从撤回重复地图给药的12到16天显着减弱了MAP预处理增加SSRI注射后13天对刺激剂量的运动反应的能力。反复治疗FLX或PRXalone failed to affect the motor stimulation following the challenge of saline and MAP 13 days later. These results suggest that the intermittent and repetitive elevation of serotonergic tone may inhibit the expression of the motor sensitization induced by pretreatment with MAP. It is proposed that clinically available serotonin reuptake inhibitors could be useful for preventing the recurrence of hallucinatory-paranoid state in drug-induced psychosis andschizophrenia。 |
| SCZ关键字 | schizophrenia |
| 2 | Neuropharmacology 2008 Nov 55: 1015-22 |
| PMID | 18655798 |
| Title | An update on the role of the 5-hydroxytryptamine6 receptor in cognitive function. |
| 抽象的 | 由于5-羟色胺（6）（5-HT（6））受体几乎仅在中枢神经系统中表达，尤其是在与学习和记忆有关的领域中，许多研究都检查了其在啮齿动物中的认知功能中的作用，如本文所述，。在健康的成年大鼠中，大多数研究报告说，5-HT（6）受体拮抗剂增强了在莫里斯水迷宫中空间学习的保留，改善了自动修饰任务和反向自然遗忘物体识别方面的巩固。拮抗剂似乎促进了胆碱能和谷氨酸能神经传递，从而逆转了cpolamine和NMDA受体拮抗剂诱导的记忆障碍。最近的报告显示，5-HT（6）受体拮抗剂，PRX-07034，恢复了在社会隔离中饲养的大鼠产生的新物体识别的损害schizophrenia。5-HT（6）受体拮抗剂RO 04-6790，在水迷宫中孤立地饲养但没有群体的对照中，适度改善了逆转学习。RO 04-6790还改善了在接受慢性间歇性苯二酮和药物为18个月大的大鼠的成年大鼠中的新颖对象歧视。但是，有关它们在动物模型中的影响的更多信息schizophreniaand Alzheimer's disease is required. Several selective high-affinity 5-HT(6) receptor agonists developed recently also improve object discrimination and extra-dimensional set-shifting behaviour. Thus both 5-HT(6) receptor agonist and antagonist compounds show promise as pro-cognitive agents in pre-clinical studies but the explanation for their paradoxical analogous effect is currently unclear, and is discussed in this article. |
| SCZ关键字 | schizophrenia |
| 3 | J Chem Inf Model 2011 Feb 51: 420-33 |
| PMID | 21299232 |
| Title | 与5-羟色胺5-HT2B和5-HT2C受体结合的激动剂和拮抗剂的预测结构和动力学。 |
| 抽象的 | 亚型2-羟色胺（5-羟色胺，5-HT）受体是主要药物靶标schizophrenia, feeding disorders, perception, depression, migraines, hypertension, anxiety, hallucinogens, and gastrointestinal dysfunctions. (1) We report here the predicted structure of 5-HT2B and 5-HT2C receptors bound to highly potent and selective 5-HT2B antagonistPRX-08066 3，（PKI：30 nm），包括关键结合残基[V103（2.53），L132（3.29），V190（4.60）和L347（6.58）]确定与5-HT2B结合在5-HT2B上的选择性ht2a。我们还报告了内源激动剂（5-HT）和HT2B选择性拮抗剂2（1-甲基-1-1,6,7,8-四氢 - 吡咯烷[2,3-G] quinoline-5-羧酸的结构吡啶-3-酰胺）。我们检查了显式膜和水中的激动剂和拮抗剂结合的HT2B受体的动力学，并发现水迁移到NPXXY基序中，以及与D（E）Ry区域离子锁的稳定性相关的结合位点的不同模式。 |
| SCZ关键字 | schizophrenia |
| 4 | Psychopharmacology (Berl.) 2012 Apr 220: 687-96 |
| PMID | 21989804 |
| Title | 新型5-HT6拮抗剂PRX-07034对大鼠认知灵活性和工作记忆的影响。 |
| 抽象的 | Accumulating evidence indicates thatschizophrenia自闭症谱系障碍患者的工作记忆和策略切换中的认知缺陷为特征。有积极的证据表明，5-羟化性胺（5-HT）（6）受体可能是改善认知功能的有用靶标。 在目前的实验中，新颖的5-HT（6）拮抗剂，PRX-07034检查了其对5-HT（6）受体的选择性，及其对延迟自发交替和策略切换的影响。 The binding affinity ofPRX评估了5-HT（6）受体，其他5-HT受体以及其他G蛋白偶联受体，离子通道和转运蛋白的-07034。从转染的HEK-293细胞中测量了环状AMP的产生。在不同的行为实验中，大鼠接受了不同的剂量PRX-07034（0.1、1或3.mg/kg，i.p.）30 min在延迟自发交替测试之前或在采集和开关阶段之前，请在位置响应开关测试中进行。 结果表明PRX-07034是否有效（Ki？=？4-8 nm）和高度选择性的5-HT（6）受体拮抗剂（对5-HT（6）受体的100倍选择性，而其他68个GPCR，离子，离子d（3）（ki？=？71 nm）和5-HT（1b）（ki？=？260 nm）受体除外的通道和转运蛋白。用于环状AMP定量，PRX-07034 demonstrated antagonist activity (IC(50)?=?19�nM) without an effect on basal levels and did not show any agonist activity up to 10�?M.PRX-07034在1和3米克/千克（但不是0.1 mg/kg）时显着增强了延迟的自发交替。1和3 mg/kg的药物也增强了位置和响应策略之间的切换，但不影响对位置或响应区分的初始学习。 这些发现表明PRX-07034 is a selective 5-HT(6) receptor antagonist that may represent a novel treatment for enhancing working memory and cognitive flexibility. |
| SCZ关键字 | schizophrenia |
| 5 | Handb exp Pharmacol 2012 -1 -1：147-65 |
| PMID | 23027415 |
| Title | 5-HT（2C）激动剂作为治疗精神分裂症的治疗剂。 |
| 抽象的 | The 5-HT(2C) receptor is a highly complex, highly regulated receptor which is widely distributed throughout the brain. The 5-HT(2C) receptor couples to multiple signal transduction pathways leading to engagement of a number of intracellular signaling molecules. Moreover, there are multiple allelic variants of the 5-HT(2C) receptor and the receptor is subject to RNA editing in the coding regions. The complexity of this receptor is further emphasized by the studies suggesting the utility of either agonists or antagonists in the treatment ofschizophrenia。虽然几种5-HT（2C）激动剂已经表现出肥胖症的临床功效（洛卡塞蛋白，，PRX-000933），本次审查的重点是5-HT（2C）激动剂的治疗潜力schizophrenia。为此，来自神经化学，电生理学和行为视角的5-HT（2C）激动剂的临床前谱表明抗精神病药样疗效，没有锥体外症状或体重增加。最近，选择性5-HT（2C）激动剂Vabicaserin在II期试验中表现出临床功效schizophrenia没有体重增加且EPS责任低的患者。这些数据令人鼓舞，并表明5-HT（2C）激动剂是治疗精神疾病的潜在疗法。 |
| SCZ关键字 | schizophrenia |
| 6 | 能。J. Physiol。Pharmacol。2015年1月93日：13-21 |
| PMID | 25429515 |
| Title | Low-dose prazosin in combination with 5-HT6 antagonist PRX-07034 has antipsychotic effects. |
| 抽象的 | An extensive amount of research has focused on the development of new pharmacological agents to treatschizophrenia。Varying from person to person,schizophrenia是一种异质性疾病，具有正，阴性和认知缺陷的症状。PRX-07034, a 5-hydroxytryptamine6 (5-HT6) receptor antagonist has been evaluated for its potential in treating obesity and cognitive deficits. This study evaluatedPRX-07034 (0.1, 0.3, and 1.0 mg/kg body mass, by intraperitoneal (i.p.) injection), in combination with a low dose of prazosin (0.3 mg/kg, i.p.), for its antipsychotic potential. The research utilized a stereotypy assay, an open field test, an object recognition task, and prepulse inhibition. Dizocilpine, a non-competitive N-methyl-d-aspartate (NMDA) antagonist, was also administered in the above-mentioned assays as a psychomimetic. The combination ofPRX-07034 and prazosin alleviated stereotypy and hyperlocomotor activity while enhancing memory in an object recognition task, and reversed sensory-gating deficits induced by dizocilpine. Examination of the medial prefrontal cortex revealed that a combination ofPRX-07034和prazosin降低了5-HT的二唑磺胺介导的增加。这些结果表明，与低剂量的prazosin的5-HT6拮抗剂的组合可以在治疗中具有治疗潜力schizophrenia。 |
| SCZ关键字 | schizophrenia |