CN117357503A - 对羟基苯乙酰胺在治疗精神疾病中的应用 - Google Patents
对羟基苯乙酰胺在治疗精神疾病中的应用 Download PDFInfo
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- CN117357503A CN117357503A CN202311680393.0A CN202311680393A CN117357503A CN 117357503 A CN117357503 A CN 117357503A CN 202311680393 A CN202311680393 A CN 202311680393A CN 117357503 A CN117357503 A CN 117357503A
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- hydroxyphenylacetamide
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- anxiety
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Abstract
本发明公开了对羟基苯乙酰胺在治疗精神疾病中的应用。本发明发现对羟基苯乙酰胺可以改善因高原低氧诱发的焦虑样行为,为高原低氧条件下诱发的情绪障碍提供了一种可能的干预制剂。
Description
技术领域
本发明属于生物医药领域,具体涉及对羟基苯乙酰胺在治疗精神疾病中的应用。
背景技术
精神疾病的表现是人的精神活动异常,如思维紊乱、情感波动失常,多数病人容易复发,病程较长。据统计,我国有近两千万的精神疾病患者。
在精神疾病中,抑郁症和焦虑症均是发病率较高,且容易复发的精神疾病。抑郁症和焦虑症均会严重影响患者的工作和生活,随着社会压力的增加,抑郁症和焦虑症的患病率均呈逐年上升趋势。
目前,临床上常用的抗抑郁和抗焦虑的药物为坦度螺酮、丁螺环酮、氟西汀和帕罗西汀等,且药物治疗是治疗抑郁症和焦虑症的主要手段。但是,目前的临床治疗药物效果不佳,不能有效实现抗抑郁和抗焦虑的作用。因此,寻找新的治疗药物势在必行。
发明内容
为弥补现有技术的不足,本发明提供了对羟基苯乙酰胺在治疗精神疾病中的应用。
为实现上述目的,本发明采用如下技术方案:
本发明的第一方面提供了对羟基苯乙酰胺在制备治疗精神疾病的药物中的应用。
进一步,所述精神疾病选自情绪障碍。
进一步,所述情绪障碍选自焦虑。
进一步,所述焦虑为高原低氧诱发的焦虑。
进一步,所述对羟基苯乙酰胺还包括其药学上可接受的盐。
进一步,所述药物还包括药学上可接受的载体。
进一步,所述药学上可接受的载体包括稀释剂、粘合剂、表面活性剂、致湿剂、吸附载体、润滑剂、填充剂、崩解剂。
本发明的第二方面提供了一种治疗精神疾病的药物,所述药物包括对羟基苯乙酰胺或其药学上可接受的盐。
进一步,所述药物还包括其他治疗精神疾病的药物。
进一步,所述其他治疗精神疾病的药物包括其他抗焦虑的药物和/或其他抗抑郁的。
进一步,所述其他治疗精神疾病的药物选自其他抗焦虑的药物。
进一步,所述其他抗焦虑的药物包括所述其他抗焦虑的药物包括苯二氮卓类、氨甲酸酯类、氮杂螺酮类或二苯甲烷类中的一种或多种。
进一步,苯二氮卓类药物包括利眠宁、氯氮卓、地西泮、氟西泮、氟地西泮、硝西泮、氟硝西泮、普拉西泮、劳拉西泮、洛美西泮、奥沙西泮、替马西泮、氯硝西泮、咪达唑仑、去甲羟基安定片、硝基安定片或艾司唑仑片。
进一步,氨甲酸酯类药物包括甲丙氟酯、卡立普多。
进一步,氮杂螺酮类药物包括坦度螺酮、丁螺环酮。
进一步,二苯甲烷类药物包括定泰乐。
本发明的优点和有益效果:
本发明发现对羟基苯乙酰胺可以改善因高原低氧诱发的焦虑样行为,为高原低氧条件下诱发的情绪障碍提供了一种可能的干预制剂。
附图说明
图1是旷场实验结果图,其中,1A是区域活动距离统计图,1B是区域活动时间统计图,1C是进入中心区域的次数统计图,1D是旷场实验结果图;
图2是高架十字迷宫实验结果图,其中,2A是开放臂活动距离统计图,2B是开放臂活动时间统计图,2C是进入开放臂的次数统计图,2D是高架十字迷宫实验结果图。
具体实施方式
下文提供了本说明书中使用的一些术语的定义。除非另有说明,本文中使用的所有技术和科学用语通常具有和本发明所属领域的普通技术人员通常理解的意思相同的意思。
本发明提供了对羟基苯乙酰胺在制备治疗精神疾病的药物中的应用。
在本发明的一种实施方式中,精神疾病是指与脑功能以及认知过程或行为有关的病症或疾病。精神疾病可以根据影响精神官能的神经系统疾病的类型进一步分类。精神疾病主要表现在思想、感觉、情感和/或行为异常中,从而引起困扰或功能障碍(例如,精神功能障碍、如痴呆或衰老)。因此,精神疾病有时与精神异常或精神病互换使用。
精神疾病通常以个体中发生的心理或行为方式为特征,被认为会导致正常发展或文化的一部分无法预料的困扰或残疾。精神疾病的定义、评估和分类可能会有所不同,但精神疾病专业人士广泛接受《国际疾病和相关健康问题分类》(ICD,由世界卫生组织WHO出版)或《精神疾病诊断和统计手册》(DSM,由美国精神病学协会APA出版)和其他手册中列出的准则。可以使用本领域从业医生所接受的这些出版物和其他出版物中提出的标准对个体进行各种精神疾病的评估,并且可以使用这些出版物在个体中确定精神疾病的表现和严重性。
这些方案中的诊断类别可以包括解离性疾病、情绪障碍、焦虑症、精神病、进食障碍、发育障碍、人格障碍和其他类别。存在不同类别的精神障碍,以及许多不同方面的可能变得紊乱的人类行为和性格。
第一类精神疾病包括思维和认知障碍,例如精神分裂症和谵妄。第二类精神疾病包括情绪障碍,例如情感障碍和焦虑(焦虑症)。第三类精神疾病包括社交行为障碍,例如性格缺陷和人格障碍。第四类精神疾病包括学习、记忆和智力障碍,例如智力低下和痴呆。因此,精神疾病包括精神分裂症、谵妄、注意力缺陷障碍(ADD)、精神分裂性障碍、抑郁症(例如耐锂性抑郁症)、躁狂症、注意力缺陷症、药物成瘾、痴呆、躁动、冷漠、焦虑、精神病、人格障碍、双相情感障碍、单相情感障碍、强迫症、进食障碍、创伤后应激障碍、易怒、青少年行为障碍和去抑制。
在本发明的优选的实施方式中,所述精神疾病选自情绪障碍。
在本发明的更优选的实施方式中,所述情绪障碍选自焦虑。
在本发明的一种实施方式中,焦虑或焦虑症是一种内心混乱的不愉快状态,通常伴有神经行为诸如来回踱步、躯体主诉和沉思默想。它是对预期事件的主观不愉快恐惧感,并且本身可被描述为害怕、担忧和不安感,广义上通常概括为对只在主观上视为威胁的情况的过度反应。
焦虑包括药物诱发的焦虑或环境变化诱发的焦虑,如高原低氧诱发的焦虑。
在本发明的具体实施方式中,焦虑为高原低氧诱发的焦虑。
所述对羟基苯乙酰胺还包括其药学上可接受的盐。
在本发明的一种实施方式中,药学上可接受的盐是指所公开化合物(对羟基苯乙酰胺)的衍生物,其中母体化合物通过制备其酸盐或碱盐而被修饰。代表性的药学上可接受的盐包括例如碱金属盐,碱土金属盐,铵盐,水溶性盐和水不溶性盐,例如乙酸盐,氨芪磺酸盐(amsonate)(4,4-二氨基芪-2 ,2-二磺酸盐),苯磺酸盐,苯甲酸盐,碳酸氢盐,硫酸氢盐,酒石酸氢盐,硼酸盐,溴化物,丁酸盐,钙,乙二胺四乙酸钙,樟脑磺酸盐(camsylate),碳酸盐,氯化物,柠檬酸盐,克拉维酸盐,二盐酸盐,乙二胺四乙酸盐,乙二磺酸盐,丙酸酯十二烷基硫酸盐(estolate),乙磺酸盐,富马酸盐,葡庚糖酸盐,葡萄糖酸盐,谷氨酸盐,乙醇酰基氨苯胂酸盐(glycollylarsanilate),六氟磷酸盐,己基间苯二酚盐(hexylresorcinate),海巴明(hydrabamine),氢溴酸盐,盐酸盐,羟基萘甲酸盐,碘化物,异硫代硫酸盐,乳酸盐,乳糖醛酸盐,月桂酸盐,苹果酸盐,马来酸盐,扁桃酸盐,甲磺酸盐,甲基溴化物(methylbromide),甲基硝酸盐,甲基硫酸盐,黏酸盐,萘磺酸盐,硝酸盐,N-甲基葡糖胺铵盐,3-羟基-2-萘甲酸盐,油酸盐,草酸盐,棕榈酸盐,双羟萘酸盐(pamoate)(1 ,1-亚甲基-双-2-羟基-3-萘甲酸盐,依伯酸盐(einbonate)),泛酸盐,磷酸盐/二磷酸盐,苦味酸盐,聚半乳糖醛酸盐,丙酸盐,对甲苯磺酸盐,水杨酸盐,硬脂酸盐,碱式乙酸盐(subacetate),琥珀酸盐,硫酸盐,磺基水杨酸盐,苏拉酸盐(suramate),丹宁酸盐,酒石酸盐,氯茶碱(teoclate),甲苯磺酸盐,三乙基碘(triethiodide)和戊酸盐。药学上可接受的盐在其结构中可具有多于一个带电原子。在这种情况下,药学上可接受的盐可具有多个抗衡离子。因此,药学上可接受的盐可具有一个或多个带电原子和/或一个或多个抗衡离子。
这些药学上可接受的盐通过本领域已知的方法制备,例如通过将游离胺碱与过量的酸溶解在醇水溶液中,或将游离羧酸用碱金属碱(例如氢氧化物)或用胺中和。
所述药物还包括药学上可接受的载体。
在本发明的一种实施方式中,药学上可接受的载体在Remington'sPharmaceutical Sciences(19th ed.,1995)中有详细的记载,包括但不限于稀释剂、粘合剂、表面活性剂、致湿剂、吸附载体、润滑剂、填充剂、崩解剂。这些物质根据需要用于帮助配方的稳定性或有助于提高活性或它的生物有效性或在口服的情况下产生可接受的口感或气味,在这种药物中可以使用的制剂可以是其原始化合物本身的形式或任选地使用其药物学可接受的盐的形式,如此配制的药物根据需要可选择本领域技术人员已知的任何适当的方式把药物进行给药。
其中,稀释剂包括但不限于乳糖、氯化钠、葡萄糖、尿素、淀粉、水。
粘合剂包括但不限于淀粉、预胶化淀粉、糊精、麦芽糖糊精、蔗糖、阿拉伯胶、明胶、甲基纤维素、羧甲基纤维素、乙基纤维素、聚乙烯醇、聚乙二醇、聚乙烯比咯烷酮、海藻酸及海藻酸盐、黄原胶、羟丙基纤维素和羟丙基甲基纤维素。
表面活性剂包括但不限于聚氧化乙烯山梨聚糖脂肪酸酯、十二烷基硫酸钠、硬脂酸单甘油酯、十六烷醇。
致湿剂包括但不限于甘油、淀粉。
吸附载体包括但不限于淀粉、乳糖、斑脱土、硅胶、高岭土和皂粘土。
润滑剂包括但不限于硬脂酸锌、单硬脂酸甘油酯、聚乙二醇、滑石粉、硬脂酸钙和镁、聚乙二醇、硼酸粉末、氢化植物油、硬脂富马酸钠、聚氧乙烯单硬脂酸酯、单月桂蔗糖酸酯、月桂醇硫酸钠、月桂醇硫酸镁、十二烷基硫酸镁。
填充剂包括但不限于甘露醇(粒状或粉状)、木糖醇、山梨醇、麦芽糖、赤藓糖、微晶纤维素、聚合糖、偶合糖、葡萄糖、乳糖、蔗糖、糊精、淀粉、海藻酸钠、海带多糖粉末、琼脂粉末、碳酸钙和碳酸氢钠。
崩解剂包括但不限于交联乙烯吡咯烷酮、羧甲基淀粉钠、低取代羟丙基甲基、交联羧甲基纤维素钠、大豆多糖。
在本发明的一种实施方式中,药物可以是适合注射给药的剂型、适合口服给药的剂型(如固体剂型、液体剂型、乳剂、悬液)、适合局部给药的油膏、乳膏或洗剂形式、适合用作滴眼剂的递送剂型、适合通过吸入给药的气雾剂形式(如通过鼻内吸入或口吸入)、适合胃肠外给药的剂型,即皮下、肌肉内或静脉内注射。
用于口服给药的固体剂型可包含在人和兽医药学实践中可接受的粘合剂、增甜剂、崩解剂、稀释剂、调味剂、包衣剂、防腐剂、润滑剂和/或延时剂(timedelayagent)。合适的粘合剂包括阿拉伯胶、明胶、玉米淀粉、黄耆树胶、海藻酸钠、羧甲基纤维素或聚乙二醇。合适的增甜剂包括蔗糖、乳糖、葡萄糖、阿斯巴特或糖精。合适的崩解剂包括玉米淀粉、甲基纤维素、聚乙烯吡咯烷酮、瓜尔胶、黄原胶、膨润土、藻酸或琼脂。合适的稀释剂包括乳糖、山梨醇、甘露醇、右旋糖、高岭土、纤维素、碳酸钙、硅酸钙或磷酸二钙。合适的调味剂包括薄荷油、冬青油、樱桃、柑橘或树莓调味剂。合适的包衣剂包括丙烯酸和/或甲基丙烯酸和/或它们的酯类的聚合物或共聚物、蜡、脂肪醇、玉米蛋白、虫胶或麸质。合适的防腐剂包括苯甲酸钠、维生素E、α-生育酚、抗坏血酸、对羟基苯甲酸甲酯、对羟基苯甲酸丙酯或亚硫酸氢钠。合适的润滑剂包括硬脂酸镁、硬脂酸、油酸钠、氯化钠或滑石。合适的延时剂包括单硬脂酸甘油酯或二硬脂酸甘油酯。
用于口服给药的液体剂型除了上述药物以外,还可包含液体载体。合适的液体载体包括水、油类如橄榄油、花生油、麻油、向日葵油、红花油、花生油、椰子油、液体石蜡、乙二醇、丙二醇、聚乙二醇、乙醇、丙醇、异丙醇、甘油、脂肪醇、甘油三酯或其混合物。
用于口服给药的悬液可进一步包括分散剂和/或悬浮剂。合适的悬浮剂包括羧甲基纤维素钠、甲基纤维素、羟丙基甲基纤维素、聚乙稀吡咯烷酮、海藻酸钠或乙酰乙醇。合适的分散剂包括卵磷脂、如硬脂酸之类的脂肪酸的聚氧乙烯酯类、聚氧乙烯山梨醇单-或二-油酸酯、-硬脂酸酯或-月桂酸酯、聚氧乙烯脱水山梨糖醇单-或二-油酸酯、-硬脂酸酯或-月桂酸酯和类似物。
本发明提供了一种治疗精神疾病的药物,所述药物包括对羟基苯乙酰胺或其药学上可接受的盐。
所述药物还包括其他治疗精神疾病的药物。
在本发明的一种实施方式中,其他治疗精神疾病的药物可以是有效量的抗焦虑药(包括苯二氮卓类、氨甲酸酯类、氮杂螺酮类或二苯甲烷类药物;苯二氮卓类药物包括利眠宁、氯氮卓、地西泮、氟西泮、氟地西泮、硝西泮、氟硝西泮、普拉西泮、劳拉西泮、洛美西泮、奥沙西泮、替马西泮、氯硝西泮、咪达唑仑、去甲羟基安定片、硝基安定片或艾司唑仑片;氨甲酸酯类药物包括甲丙氟酯、卡立普多;氮杂螺酮类药物包括坦度螺酮、丁螺环酮;二苯甲烷类药物包括定泰乐)、有效量的抗抑郁药(例如氟西汀、依他普仑、安非他酮、米氮平、阿米替林、丙咪嗪、文拉法辛、舍曲林、帕罗西汀或三环类抗抑郁药、选择性5-羟色胺再摄取抑制剂、5-羟色胺和去甲肾上腺素再摄取抑制剂、去甲肾上腺素和多巴胺再摄取抑制剂、氧化酶抑制剂或批准用于抑郁症的其他药物)或有效量的β-阻断剂(如醋丁洛尔、阿替洛尔、倍他洛尔、比索洛尔、艾司洛尔、奈比洛尔、美托洛尔、卡托醇、喷布洛尔、吲哚洛尔、卡维地洛、拉贝洛尔、左布诺洛尔、美替洛尔、纳多洛尔、普萘洛尔、索他洛尔、噻吗洛尔或β-肾上腺素受体的其他选择性或非选择性阻断剂)。
在本发明的一种实施方式中,对羟基苯乙酰胺或其药学上可接受的盐可以与非药物治疗组合使用,如心理疗法或脑刺激疗法。在一些实施方式中,对羟基苯乙酰胺或其药学上可接受的盐与脑刺激组合使用,所述脑刺激可以是迷走神经刺激、重复经颅磁刺激、磁性癫痫疗法,深部脑刺激或任何其他涉及通过电、磁或植入物调节脑功能的疗法。
在本发明的一种实施方式中,有效量或治疗有效量是指足以在疾病的治疗或预防中提供治疗或预防益处或足以使与疾病相关的症状延迟或降至最低程度的化合物的量。此外,关于本文所用化合物的治疗有效量是指单独的或与在疾病的治疗或预防中提供治疗益处的其他疗法组合的化合物的量。与本文使用的化合物联合使用时,该术语可包括改良整体治疗、减少或避免疾病的症状或病因、或增强另一治疗剂的治疗功效或与另一治疗剂协同的量。全部治疗效果不一定通过施用一剂(或一次剂量)而出现,可以仅在施用一系列剂量后出现。因此,可以在一次或多次施用中施用有效量。
本发明的药物的剂量方案将根据已知因素而变化,例如特定药剂的药效学特征及其施用模式和途径;接受者的人种、年龄、性别、健康、医学状况、和体重;症状的性质和程度;并行治疗的种类;治疗频率;给药途径、以及所需的效果。在某些实施方式中,本发明的药物可以以单次日剂量施用,或者总日剂量可以以每日二次、三次、或四次的分剂量施用。
在本发明的一种实施方式中,施用是指递送至作用部位的方法或途径,如将本文所公开的对羟基苯乙酰胺或其药学上可接受的盐放置至受试者中。可以通过任何适当的途径施用以增加受试者中对羟基苯乙酰胺或其药学上可接受的盐水平的包含试剂的药物,在受试者中产生有效的治疗。
在本发明的一种实施方式中,术语治疗是指减弱或减轻,或改善或根除疾病或与疾病相关的一种或多种症状。在某些实施方式中,该术语是指使疾病的扩散或恶化降至最低程度,这是由于向患有这种疾病的患者施用一种或多种预防剂或治疗剂而引起的。出于本文提供的各个方面和实施方式的目的,治疗包括但不限于减轻、缓解或改善所治疗的疾病或病症的一种或多种临床表现或副作用,改良一种或多种临床结果,降低疾病程度,延迟或减缓疾病进展,改善、缓解或稳定疾病状态,以及本文所述的其他有益结果。
下面结合具体实施例进一步阐述此发明。应理解的是,在此描述的特定实施方式通过举例的方式来表示,并不作为对本发明的限制。在不偏离本发明范围的情况下,本发明的主要特征可以用于各种实施方式。
实施例
1实验材料
C57BL/6J小鼠(北京斯贝福生物技术有限公司)、生理盐水(石家庄四药有限公司)、对羟基苯乙酰胺(HPAD,Hydroxyphenylacetamide,阿拉丁,H117443)、电子天平(Sartorius BSA224S)、1mL注射器(浙江康德莱医疗器械股份有限公司)、Smart3.0行为学分析软件(深圳瑞沃德生命科技有限公司)用于旷场、高架十字迷宫等行为学实验检测、低压低氧舱(上海塔望智能科技有限公司)。
2实验方案
准备32只6-8周龄的C57BL/6J小鼠,随机分为对照组(CON)、给药组(HPAD)、高原低氧组(HY)和高原低氧给药组(HY+HPAD),每组8只,适应性饲养7天,期间保持12h正常光照(7:00-19:00)、充足食物和饮用水。适应性饲养结束后,对照组和高原低氧组小鼠腹腔注射200uL生理盐水7天,给药组和高原低氧给药组小鼠腹腔注射200uL HPAD(50mg/kg)7天,期间保持12h正常光照(7:00-19:00)、充足食物和饮用水。给药结束后次日将高原低氧组和高原低氧给药组放入高原低氧舱模拟低氧48h(温度27.8℃,湿度60.2%,氧气20.1%,二氧化碳0.75%,大气压101.3Kpa,舱内压力47.4Kpa,差压-53.9Kpa,氧分压9.5Kpa,海拔高度6000m),其余两组保持正常饲养。高原低氧结束后对四组小鼠进行旷场和高架十字迷宫实验。
3实验结果
旷场实验结果表明,与对照组小鼠相比,给药组小鼠在旷场中心区域活动没有显著性差异,表明对羟基苯乙酰胺(50mg/kg)对正常小鼠没有负面影响,小鼠依然保持良好的自主探索行为活动。与对照组相比,高原低氧组小鼠在旷场中心区域活动减少,自主探索行为受到影响,表现出焦虑样行为。与高原低氧组相比,高原低氧给药组小鼠在旷场中心区域活动增加,自主探索行为活动得到改善(图1)。
高架十字迷宫实验结果表明,与对照组小鼠相比,给药组小鼠在高架十字迷宫开放臂活动没有显著性差异,表明对羟基苯乙酰胺(50mg/kg)对正常小鼠没有负面影响,小鼠依然保持良好的自主探索行为活动。与对照组相比,高原低氧组小鼠在高架十字迷宫开放臂活动减少,自主探索行为受到影响,表现出焦虑样行为。与高原低氧组相比,高原低氧给药组小鼠在高架十字迷宫开放臂活动增加,自主探索行为活动得到改善。因此说明对羟基苯乙酰胺可以改善因高原低氧诱发的焦虑样行为(图2)。
上述实施例的说明只是用于理解本发明的方法及其核心思想。应当指出,对于本领域的普通技术人员来说,在不脱离本发明原理的前提下,还可以对本发明进行若干改进和修饰,这些改进和修饰也将落入本发明权利要求的保护范围内。
Claims (10)
1.对羟基苯乙酰胺在制备治疗精神疾病的药物中的应用。
2.根据权利要求1所述的应用,其特征在于,所述精神疾病选自情绪障碍。
3.根据权利要求1所述的应用,其特征在于,所述情绪障碍选自焦虑。
4.根据权利要求3所述的应用,其特征在于,所述焦虑为高原低氧诱发的焦虑。
5.根据权利要求1所述的应用,其特征在于,所述对羟基苯乙酰胺还包括其药学上可接受的盐。
6.根据权利要求1所述的应用,其特征在于,所述药物还包括药学上可接受的载体。
7.一种治疗精神疾病的药物,其特征在于,所述药物包括对羟基苯乙酰胺或其药学上可接受的盐。
8.根据权利要求7所述的药物,其特征在于,所述药物还包括其他治疗精神疾病的药物。
9.根据权利要求8所述的药物,其特征在于,所述其他治疗精神疾病的药物选自其他抗焦虑的药物。
10.根据权利要求9所述的药物,其特征在于,所述其他抗焦虑的药物包括苯二氮卓类、氨甲酸酯类、氮杂螺酮类或二苯甲烷类中的一种或多种。
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Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20100261724A1 (en) * | 2007-10-24 | 2010-10-14 | Barrow James C | Heterocycle phenyl amide t-type calcium channel antagonists |
US20160022653A1 (en) * | 2014-07-22 | 2016-01-28 | Thomas P. Dooley | Methods and pharmaceutical compositions for the treatment of symptoms of anxiety and panic using beta adrenergic receptor antagonist and muscarinic receptor antagonist combinations |
CN106916073A (zh) * | 2017-01-20 | 2017-07-04 | 上海巧坤化工科技有限公司 | 一种大麦芽碱盐酸盐的合成方法 |
-
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Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20100261724A1 (en) * | 2007-10-24 | 2010-10-14 | Barrow James C | Heterocycle phenyl amide t-type calcium channel antagonists |
US20160022653A1 (en) * | 2014-07-22 | 2016-01-28 | Thomas P. Dooley | Methods and pharmaceutical compositions for the treatment of symptoms of anxiety and panic using beta adrenergic receptor antagonist and muscarinic receptor antagonist combinations |
CN106916073A (zh) * | 2017-01-20 | 2017-07-04 | 上海巧坤化工科技有限公司 | 一种大麦芽碱盐酸盐的合成方法 |
Non-Patent Citations (2)
Title |
---|
AMINE BAHI等: ""Dopamine transporter (DAT) knockdown in the nucleus accumbens improves anxiety- and depression-related behaviors in adult mice"", 《BEHAVIOURAL BRAIN RESEARCH》, vol. 359, pages 104 - 115, XP085561176, DOI: 10.1016/j.bbr.2018.10.028 * |
MICHAEL APPELL等: ""Structure–activity relationships for substrate recognition by the human dopamine transporter"", 《BIOCHEMICAL PHARMACOLOGY》, vol. 67, no. 2, pages 293 - 302 * |
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