CN115400109A - 酪胺及其衍生物在制备治疗抑郁症药物中的应用 - Google Patents
酪胺及其衍生物在制备治疗抑郁症药物中的应用 Download PDFInfo
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- CN115400109A CN115400109A CN202211199468.9A CN202211199468A CN115400109A CN 115400109 A CN115400109 A CN 115400109A CN 202211199468 A CN202211199468 A CN 202211199468A CN 115400109 A CN115400109 A CN 115400109A
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- tyramine
- depression
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Abstract
本发明提供酪胺(Tyramine)及其衍生物在制备治疗抑郁症药物中的应用。所述酪胺衍生物为酪胺盐酸盐或酪胺/双磷酸盐。所述应用剂量为每千克体重0.01‑20mg酪胺或其衍生物,给药后60分钟内即可产生抗抑郁效果。给药5天后,低剂量和高剂量均产生显著的抗抑郁效果。本发明研究结果表明,在哺乳动物小鼠悬尾实验中,酪胺或其衍生物具有快速抗抑郁症的功效,且比常规抗抑郁药物丙咪嗪更有效。本发明采用强迫游泳实验和小鼠悬尾实验作为药物筛选实验,同时进行了小鼠开野实验(Open field test),以检验小鼠的自主活动性,避免了中枢兴奋药的干扰。本发明制备的药物抗抑郁效果显著、起效快、用药量少、副作用小,有望成为快速、高效、新机制的抗抑郁新药。
Description
技术领域
本发明属于医药技术领域,涉及酪胺(Tyramine)及其衍生物在制备治疗抑郁症药物中的应用及所制备的抗抑郁药物。
背景技术
重性抑郁障碍(Major depressive disorder,MDD)是一种严重的、反复发作的致残性精神疾病。全球范围内有大约3亿人受抑郁症困扰。中国的抑郁症发病率为4.2%,有大约5600万抑郁症患者。抑郁症是导致因伤残寿命损失(年)的第二大主要原因,已成为迫切需要解决的重大公共卫生问题。抑郁症临床可见心境低落、情绪消沉、自卑抑郁,甚至悲观厌世,有自杀企图或行为等。目前临床上一线的抗抑郁药主要包括选择性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等,但使用这类药物起效慢,作用谱窄,停药后易复发。虽然使用多种抗抑郁药物治疗,但仍有约30%的患者会成为难治性抑郁症(Treatment-resistant Depression,TRD)。这类难治型抑郁症病人存在着更高的社会负担风险和自杀风险。因此,寻找新的依从性好、副作用少、具有新型药理机制的抗抑郁症药物具有广泛临床需求,也是目前国际研究的热点。
酪胺(Tyramine)是一种生物碱成分,熔点为175-181℃,分子式为C8H11NO,分子量为137.18,溶于氯仿、甲醇、乙醇。
亚急性毒性实验证明,酪胺对大鼠的骨髓、肝、肾等功能均无明显影响。
目前尚未见到酪胺作为活性成分预防或治疗抑郁症的报道。
发明内容
本发明的目的是提供一种酪胺及其衍生物在制备治疗抑郁症药物中的应用,这种药物具有抗抑郁效果显著、起效快、用药量少、副作用小等优点。
本发明提供式(I)酪胺或其衍生物在制备治疗抑郁症药物中的应用,
进一步,所述酪胺衍生物为酪胺盐酸盐或酪胺/双磷酸盐。
进一步,所述应用剂量为每千克体重0.01-20mg酪胺或其衍生物。
本发明还提供一种抗抑郁症药物,所述药物成分包括:酪胺或其衍生物,以及制药学上可接受的辅助成分。
进一步,所述药物成分还包括同时施用后对治疗抑郁症有积极作用的药物成分。
进一步,所述同时施用后对治疗抑郁症有积极作用的药物成分为:三环类抗抑郁药TCA、选择性五羟色胺再摄取抑制剂SSRI、五羟色胺及去甲肾上腺素再摄取抑制剂SNRI、去甲肾上腺素能和特异性5-HT受体拮抗剂NASSA、5-HT拮抗和再摄取抑制剂、或褪黑素及5-HT2C受体拮抗剂。
所述三环类抗抑郁药(TCA),包括阿米替林、丙米嗪、氯丙嗪、多塞平或氯米帕明等。
所述选择性五羟色胺再摄取抑制剂(SSRI)包括:氟西汀(百优解)、帕罗西汀(赛乐特)、氟伏沙明(fluvoxamine,兰释)、舍曲林(sertraline,左洛复)、西酞普兰(citalopram,西普妙)或艾司西酞普兰(escitalopram,来士普)等。
所述五羟色胺及去甲肾上腺素再摄取抑制剂(SNRI),包括:文拉法辛或度洛西汀等。
所述去甲肾上腺素能和特异性5-HT受体拮抗剂(NASSA),包括:米氮平等。
所述5-HT拮抗和再摄取抑制剂:如奈法唑酮或曲唑酮。
所述褪黑素及5-HT2C受体拮抗剂:如阿戈美拉汀。
进一步,所述同时施用后对治疗抑郁症有积极作用的药物成分为草药类,草药类如:圣约翰草,(St.Jonh’s wort)和噻奈普汀、伏硫西汀(又称沃替西汀,Vortioxetine)或安非他酮(Bupropion)等。
进一步,所述同时施用后对治疗抑郁症有积极作用的药物成分为:氯胺酮类,所述氯胺酮类包括S-氯胺酮或氯胺酮鼻饲剂。
进一步,所述药物药效剂量为每千克体重0.01-20mg酪胺及其衍生物。
上述药物剂型为粉剂、颗粒剂、片剂、胶囊剂、丸剂、口服液或注射液。
酪胺为白色粉末。
本发明的药物可以单位剂量形式给药,给药剂型可以是液体剂型、固体剂型。如液体剂型可以是真溶液类、胶体类、微粒剂型、乳剂剂型、混悬剂型。其他剂型例如片剂、胶囊、滴丸、气雾剂、丸剂、粉剂、溶液剂、混悬剂、乳剂、颗粒剂、栓剂、冻干粉针剂等。
给药途径可为肠道或非肠道,如口服、肌肉、皮下、鼻腔、口腔粘膜、皮肤、腹膜或直肠等。
本发明药物给药途径可为注射给药。注射包括静脉注射、肌肉注射、皮下注射、皮内注射和穴位注射等。
本发明药物可以制成普通制剂、也可以是缓释制剂、控释制剂、靶向制剂及各种微粒给药系统。
为了将单位给药剂型制成片剂,可以广泛使用本领域公知的各种载体。载体中:稀释剂与吸收剂,如淀粉、糊精、硫酸钙、乳糖、甘露醇、蔗糖、氯化钠、葡萄糖、尿素、碳酸钙、白陶土、微晶纤维素、硅酸铝等;湿润剂与粘合剂,如水、聚乙二醇、乙醇、丙醇、淀粉浆、糊精、糖浆、蜂蜜、葡萄糖溶液、阿拉伯胶浆、明胶浆、羧甲基纤维素钠、紫胶、甲基纤维素、磷酸钾、聚乙烯吡咯烷酮等;崩解剂,例如干燥淀粉、海藻酸盐、琼脂粉、褐藻淀粉、碳酸氢钠与枸橼酸、碳酸钙、聚氧乙烯山梨糖醇脂肪酸酯、十二烷基磺酸钠、甲基纤维素、乙基纤维素等;崩解抑制剂,例如蔗糖、三硬脂酸甘油酯、可可脂、氢化油等;吸收促进剂,例如季铵盐、十二烷基硫酸钠等;润滑剂,例如滑石粉、二氧化硅、玉米淀粉、硬脂酸盐、硼酸、液体石蜡、聚乙二醇等。还可将片剂进一步制成包衣片,例如糖包衣片、薄膜包衣片、肠溶包衣片,或双层片和多层片。
为了将给药单元制成丸剂,可以广泛使用本领域公知的各种载体。载体中:例如稀释剂与吸收剂,如葡萄糖、乳糖、淀粉、可可脂、氢化植物油、聚乙烯吡咯烷酮、Gelucire、高岭土、滑石粉等;粘合剂,如阿拉伯胶、黄蓍胶、明胶、乙醇、蜂蜜、液糖、米糊或面糊等;崩解剂,如琼脂粉、干燥淀粉、海藻酸盐、十二烷基磺酸钠、甲基纤维素、乙基纤维素等。
为了将给药单元制成栓剂,可以广泛使用本领域公知的各种载体。载体中:例如聚乙二醇、卵磷脂、可可脂、高级醇、高级醇的酶、明胶、半合成甘油酶等。
为了将给药单元制成胶囊,将有效成分与上述的各种载体混合,并将由此得到的混合物置于硬的明胶胶囊或软胶囊中。也可将有效成分制成微囊剂,混悬于水性介质中形成混悬剂,亦可装入硬胶囊中或制成注射剂应用。
例如,将本发明的组合物制成注射用制剂,如溶液剂、混悬剂溶液剂、乳剂、冻干粉针剂,这种制剂可以是含水或非水的,可含一种和/或多种药效学上可接受的载体、稀释剂、粘合剂、润滑剂、防腐剂、表面活性剂或分散剂。如稀释剂可选自水、乙醇、聚乙二醇、1,3一丙二醇、乙氧基化的异硬脂醇、多氧化的异硬脂醇、聚氧乙烯山梨醇脂肪酸酶等。另外,为了制备等渗注射液,可以向注射用制剂中添加适量的氯化钠、葡萄糖或甘油,此外,还可以添加常规的助溶剂、缓冲剂、pH调节剂等。这些辅料是本领域常用的。
此外如需要,也可以向药物制剂中添加着色剂、防腐剂、香料、矫味剂、甜味剂或其它材料。
本发明药用组合物的给药剂量取决于许多因素,例如所要预防或治疗疾病的性质和严重程度,患者或动物的性别、年龄、体重、性格及个体反应,给药途径、给药次数等,因此本发明的治疗剂量可以有大范围的变化。一般来讲,本发明化合物使用剂量是本领域技术人员公知的。可以根据本发明药用组合物中最后的制剂中所含有的实际有效药物数量,加以适当的调整,以达到其治疗有效量的要求。
本发明所提供的抗抑郁症药物,所述抗抑郁症包括预防和治疗两个阶段。在预防阶段本发明抗抑郁症药物的用量为:每天每千克体重0.001-3mg;在治疗阶段本发明抗抑郁症药物的用量为:每天每千克体重提供0.01-20mg酪胺(Tyramine)及其衍生物。所述抗抑郁症药物的给药方式为口服、鼻喷、滴注或注射;给药对象为哺乳动物,所述哺乳动物包括人。
本发明提供的抗抑郁症药物,以每千克体重0.01-20mg酪胺(Tyramine)及其衍生物的给药剂量;给药后60分钟内即可产生抗抑郁效果。给药5天后,低剂量和高剂量均产生显著的抗抑郁效果。这种药物具有抗抑郁效果显著、起效快、用药量少、副作用小等优点。在哺乳动物小鼠强迫游泳实验中,酪胺(Tyramine)及其衍生物比常规抗抑郁药物丙咪嗪的抗抑郁效果更加显著。
与现有技术相比,本发明的有益技术效果在于:
1.本发明提供酪胺(Tyramine)或其衍生物在制备抗抑郁症药物中的应用。本发明研究结果表明,在哺乳动物小鼠悬尾实验中,酪胺(Tyramine)或其衍生物具有快速抗抑郁症的功效,且比常规抗抑郁药物丙咪嗪更有效。
2.本发明采用强迫游泳实验和小鼠悬尾实验作为药物筛选实验。强迫游泳实验和小鼠悬尾实验,是常用的两种动物行为绝望抑郁症模型实验,能较好地保证筛选结果的可靠性。小鼠强迫游泳实验已用于很多抗抑郁药物的筛选。而且大多数有临床治疗作用的抗抑郁药也被证实在强迫游泳实验中能有效减少不动时间。
所谓不动是指“动物在水中停止挣扎,或呈漂浮状态,仅露出鼻孔保持呼吸,仅有细小的肢体运动,以保持头部浮在水面”。在试验前给予拟筛选的药物。由于动物在强迫状态下游泳使动物不能逃出恶劣环境,导致动物行为绝望。此种模型方法简便,可靠,已广泛用于抗抑郁药剂的筛选和评价。小鼠悬尾实验是小鼠在悬尾状态下不再挣扎,呈现特有的安静不动状态,抗抑郁药可明显缩短不动状态的持续时间。试验时,将小鼠尾部固定、倒悬。勿使小鼠尾部扭曲折叠。计录不动时间。不动指标为:“动物肢体和躯体未扭动挣扎”。悬尾实验对各种抗抑郁药均很敏感,而且避免了游泳实验中温度和动物运动功能障碍的干扰,因而在用一些鼠种筛选抗抑郁药物时,可以有效地验证和补充强迫游泳实验的结果。
3.比丙咪嗪显示出更强的抗抑郁效果。在小鼠动物模型悬尾实验中发现,酪胺(Tyramine)及其衍生物高剂量组小鼠(10mg/kg)在注射后60分钟抑郁症状开始缓解,即活动量相对空白对照组越来越频繁,明显缩短不动时间。注射5天后酪胺(Tyramine)及其衍生物开始明显缩短悬尾不动时间。酪胺(Tyramine)及其衍生物在剂量(10mg/kg)低于丙咪嗪(15mg/kg)的情况下,比丙咪嗪显示出更强的抗抑郁效果。
4.本发明同时进行了小鼠开野实验(Open field test),以检验小鼠的自主活动性,避免中枢兴奋药的干扰。由于经典抑郁动物模型中动物不动时间的缩短可能是由于药物的中枢兴奋性作用所引起,因此本发明还同时进行了小鼠开野实验。结果表明,与对照组相比,高浓度酪胺(Tyramine)及其衍生物对小鼠自主活动无显著影响,故可排除兴奋剂引起躁狂的可能性,证明酪胺(Tyramine)及其衍生物确实具有显著的抗抑郁作用。
5.本发明以酪胺(Tyramine)或其衍生物为有效成分的抗抑郁药物,有望成为快速、高效、新机制的抗抑郁新药。
附图说明
图1.酪胺(Tyramine)结构式;
图2.酪胺(Tyramine)的1H NMR;
图3.酪胺(Tyramine)的13C NMR;
图4.酪胺(Tyramine)的MS;
图5.酪胺(Tyramine)注射一小时后对小鼠悬尾实验的影响;
纵坐标:悬尾实验小鼠不动时间(s),横坐标:从左到右依次为DMSO对照组,酪胺(Tyramine)低剂量组(HDN-L,5mg/kg),酪胺(Tyramine)高剂量组(HDN-H,10mg/kg),丙咪嗪阳性对照组(15mg/kg)。
图6.酪胺(Tyramine)注射5天后对小鼠游泳实验的影响
纵坐标:强迫游泳实验小鼠不动时间(s),横坐标:从左到右依次为:DMSO对照组,酪胺(Tyramine)低剂量组(HDN-L,5mg/kg),酪胺(Tyramine)高剂量组(HDN-H,10mg/kg),丙咪嗪阳性对照组(IMI,15mg/kg)。
具体实施方式
以下通过具体实施例对本发明进行详细说明,需要理解的是,下述实施例仅作为解释和说明,不以任何形式限制本发明的范围。下述实施方式中,未特别说明的生物化学试剂均为本领域常规试剂,可以按照本领域常规方法配制而得或商购获得,规格为实验室纯级即可。
酪胺(Tyramine),CAS号:60-19-5,本实验室自制。
实施例1:
将100mL无水二氯甲烷,35.3g(0.26mol)三氯化铝,12.5g(0.132mol)氨基乙腈盐酸盐和12.5g(0.133mol)苯酚依次加入反应体系中,室温搅拌12h。中止反应,回收二氯甲烷,然后加水100mL,过滤,得17.8g黄色固体,即对羟基苯乙酮胺盐酸盐,m.p.241-243℃,收率72%;将10g(0.11mol)对羟苯乙酮胺盐酸盐,10%钯碳0.9g,14mL浓盐酸和100mL水投入氢化瓶中,启动搅拌,抽去反应体系中的空气后,用氮气置换1次,再次真空抽除氮气,然后在剧烈搅拌下通入氢气,室温反应9h后,放空,抽滤,滤液减压浓缩至固体析出,冰水冷却,过滤,丙酮洗,干燥得7.4g白色固体,即酪胺(Tyramine)。熔点为175-181℃,分子式为C8H11NO,分子量为137.18,溶于氯仿、甲醇、乙醇。
实施例2:
取酪胺200g及辅料适量,过筛,混匀,装入胶囊,制成10000粒酪胺胶囊。根据定量分析获得酪胺的含量,作为服用量的依据。
实施例3:
取酪胺200g加水稀释并用甜菊甙矫味而制成1%的液体药剂,制成酪胺口服液。根据定量分析获得酪胺的含量,作为服用量的依据。
实施例4:
取酪胺100克,溶于500毫升无水乙醇中,滴加3%的稀盐酸溶液,至pH=6,放置析出酪胺盐酸盐结晶,过滤,干燥,得到酪胺盐酸盐;按常规加注射液用水,精滤,灌封、灭菌制成注射液,酪胺盐酸盐含量控制在0.001-20mg/ml。
实施例5:
酪胺,按其与赋形剂重量比加入赋形剂,制成粉剂,其中酪胺含量控制在0.005-40mg/g。
实施例6:
酪胺,按其与赋形剂重量比加入赋形剂,制粒压片,其中酪胺含量控制在0.005-40mg/g。
实施例7:
取酪胺50克,溶于300毫升无水乙醇中,滴加3%的磷酸乙醇溶液,至pH=6,放置后,析出结晶,过滤,干燥,得到酪胺/双磷酸盐;按常规口服液制法制成口服液,口服液中酪胺/双磷酸盐含量控制在0.001-20mg/ml。
实施例8:
酪胺,按其与赋形剂重量比加入赋形剂,制成胶囊或颗粒剂或冲剂,其中酪胺含量控制在0.001-3mg/g。
实施例9:
酪胺,按其与赋形剂重量比加入赋形剂,制成胶囊或颗粒剂或冲剂,其中酪胺含量控制在0.01-20mg/g。
实施例10:
酪胺5克,加入淀粉1200克,乳糖400克,薄荷醇6克,羧甲基淀粉钠389克,制成含片,作为功能食品。
试验例1.酪胺(Tyramine)对动物抑郁模型悬尾实验的影响
实验动物:C57BL/6种小鼠,雄性,重量30-40克,由斯贝福(北京)生物技术有限公司提供,许可证号:SCXK(京)2019-0010。动物分笼饲养,明暗周期12h/12h,室温20~22℃,食水自由,饲料由华大蛋白实验动物中心提供。实验药品:酪胺(Tyramine)由中国医学科学院药物研究所提取,其化学纯度和结构分析如图1、2、3、4所示。盐酸丙咪嗪(Imipraminehydrochloride)为Sigma公司产品,货号I7379,批号O56K1380。实验器材:横杆;胶布;摄像机(华为手机);JUNSO多功能计时器。实验步骤:雄性C57BL/6小鼠经适应性饲养一周,分成4组,每组6-7只。分别为二甲基亚砜DMSO对照组(DMSO溶于生理盐水)、酪胺(Tyramine)低剂量组(HDN-L,5mg/kg,溶于DMSO)、酪胺(Tyramine)高剂量组(HDN-H,10mg/kg,溶于DMSO)、传统抗抑郁药物丙咪嗪阳性对照组(15mg/kg丙咪嗪,2%DMSO生理盐水溶解)。上午10时按0.1ml/10g体重腹腔注射给药,注射60分钟后,每组6-7只小鼠进行悬尾实验;小鼠悬尾实验时,用胶布将小鼠尾在距尾尖2厘米处粘在一根水平横杆上,使动物成倒挂状态,其头部离桌面约15厘米。观察6分钟,记录后4分钟内的累计不动时间。不动指标为:动物肢体和躯体均不做挣扎。统计方法:实验结果用均值±SE表示,三个样本用ANOVA检验。两个样本(丙咪嗪和生理盐水)平均数比较用t检验。酪胺(Tyramine)高剂量组小鼠在注射后60分钟抑郁症状开始缓解,即挣扎活动相对空白对照组越来越频繁,明显缩短不动时间。而丙咪嗪阳性对照组在注射后60分钟内,活动量与生理盐水对照组也有增强尚未达到显著。注射60分钟后观察结果,结果:C57BL/6雄性小鼠经不同剂量的酪胺(Tyramine)腹腔注射60分钟后,高剂量组(10mg/kg)在小鼠悬尾实验中显示出显著的抗抑郁效果(每组动物N=6-7,ANOVA检验p<0.05,**p<0.01)。如图5所示,酪胺(Tyramine)的高剂量组和低剂量组小鼠的不动时间与DMSO对照组相比由106.8±22.73s降低为66.29±14.71s(**P<0.01)和66.93±15.81s(**P<0.01),结果表明,酪胺(Tyramine)在很短的时间内即可起效,可以对抗小鼠因强迫悬尾造成的抑郁绝望症状。
试验例2.酪胺(Tyramine)对动物抑郁模型强迫游泳实验的影响
实验动物:C57BL/6种小鼠,雄性,由斯贝福(北京)生物技术有限公司提供,许可证号:SCXK(京)2019-0010。实验前一周将动物分笼饲养,明暗周期12h/12h,室温20~22℃,食水自由,饲料由华大蛋白实验动物中心提供。实验药物:酪胺(Tyramine)由中国医学科学院药物研究所提供。丙咪嗪为Sigma公司产品,货号I7379,批号O56K1380。实验仪器:玻璃圆筒(高40cm,直径14cm);小鼠开阔箱(长和宽分别为50cm,高40cm,底部16等分);温度计;JUNSO多功能计时器。
实验步骤:药物准备同悬尾实验。动物药物注射:C57BL/6小鼠,年龄7周,重量30-40克,适应环境一周后开始实验。动物随机分组,共有4组,每组6-7只动物。每天上午10点开始腹腔注射。注射量为0.3毫升/30克,每天腹腔注射一次,注射五天后开始强迫游泳实验。强迫游泳实验:将各组C57BL/6鼠单个垂直地放入有机玻璃圆筒中(40cm高×14cm直径),水深25cm,水温21-23℃。各给药组和对照组录像6分钟,比较各组小鼠在后4分钟内的累计不动时间。不动时间判定:小鼠漂浮在水面,不努力爬出圆筒,仅做一些必须保持其头部在水面的动作。
统计分析方法:实验结果用均值±SE表示,两个样本平均数比较用t检验。结果:C57BL/6雄性小鼠经不同剂量的酪胺(Tyramine)腹腔注射五天后,在小鼠强迫游泳实验中显示出极显著抗抑郁效果。这个抗抑郁效果和传统抗抑郁药物丙咪嗪相比有更强的趋势(每组动物N=6-7,*t检验p<0.05,**p<0.01)。如图6所示,与DMSO对照组比较,酪胺(Tyramine)高剂量组和低剂量组小鼠强迫游泳4分钟内的不动时间均有显著缩短,酪胺(Tyramine)低剂量组和高剂量组小鼠的不动时间与1%DMSO对照组相比,由49.22±22.27s降低为21.06±14.48s(**p<0.01)和16.46±8.42s(**p<0.01),分别缩短了57.21%和66.56%。和传统抗抑郁药丙咪嗪(降低48.94%)相比,酪胺(Tyramine)的抗抑郁作用更强。
试验例3.小鼠开野实验:
由于经典抑郁动物模型中的动物不动时间的缩短可能是由于药物的中枢兴奋性作用引起,所以本发明进行了小鼠开野实验来检验酪胺(Tyramine)的中枢兴奋性。将小鼠放入开阔箱的中间后录像6分钟。实验结果显示,小鼠在开阔箱中后5分钟运动的总距离在酪胺(Tyramine)高剂量和低剂量处理后分别为(11.50±1.69m)和(15.61±8.68m)与对照组(11.64±1.25m)相比,无明显变化(Anova,p>0.05,N=21),故可排除其引发躁狂状态的可能性,因此,酪胺(Tyramine)确实具有显著的抗抑郁效果。
最后说明的是,以上实施例仅用以说明本发明的技术方案而非限制,尽管参照较佳实施例对本发明进行了详细说明,本领域的普通技术人员应当理解,可以对本发明的技术方案进行修改或者等同替换,而不脱离本技术方案的宗旨和范围,其均应涵盖在本发明的权利要求范围当中。
Claims (9)
2.根据权利要求1所述的应用,其特征在于,所述酪胺衍生物为酪胺盐酸盐或酪胺/双磷酸盐。
3.根据权利要求1所述的应用,其特征在于,所述应用剂量为每千克体重0.01-20mg酪胺或其衍生物。
4.一种抗抑郁症药物,其特征在于,所述药物成分包括:酪胺或其衍生物,以及制药学上可接受的辅助成分。
5.根据权利要求3所述的抗抑郁症药物,其特征在于,所述药物成分还包括同时施用后对治疗抑郁症有积极作用的药物成分。
6.根据权利要求4所述的抗抑郁症药物,其特征在于,所述同时施用后对治疗抑郁症有积极作用的药物成分为:三环类抗抑郁药TCA、选择性五羟色胺再摄取抑制剂SSRI、五羟色胺及去甲肾上腺素再摄取抑制剂SNRI、去甲肾上腺素能和特异性5-HT受体拮抗剂NASSA、5-HT拮抗和再摄取抑制剂或褪黑素及5-HT2C受体拮抗剂。
7.根据权利要求4所述的抗抑郁症药物,其特征在于,所述同时施用后对治疗抑郁症有积极作用的药物成分为圣约翰草、噻奈普汀、伏硫西汀或安非他酮。
8.根据权利要求4所述的抗抑郁症药物,其特征在于,所述同时施用后对治疗抑郁症有积极作用的药物成分为S-氯胺酮或氯胺酮鼻饲剂。
9.根据权利要求4、5、6、7或8所述的抗抑郁症药物,其特征在于,所述药物剂型为粉剂、颗粒剂、片剂、胶囊剂、丸剂、口服液、或注射液。
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