CN1222291C - 联合的5-ht1a激动剂和5-羟色胺再摄取抑制剂的新用途 - Google Patents
联合的5-ht1a激动剂和5-羟色胺再摄取抑制剂的新用途 Download PDFInfo
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Abstract
作为联合的选择性5-羟色胺(5-HT)再摄取抑制剂(SSRIs)和5-HT1A受体激动剂的化合物,特别是1-[4-(5-氰基吲哚-3-基)丁基]-4-(2-氨基甲酰基-苯并呋喃-5-基)-哌嗪或其生理上可接受的盐或3-{4-[4-(4-氰基-苯基)-哌嗪-1-基]-丁基}-1H-吲哚-5-腈或其生理上可接受的盐用于制备治疗或预防与行为应激物有关的自我控制性创伤障碍和与行为应激物有关的强迫症的兽药的用途。
Description
本发明涉及作为联合的选择性5-羟色胺(5-HT)再摄取抑制剂(SSRIs)和5-HT1A受体激动剂的化合物用于制备治疗或预防与行为应激物有关的障碍的兽药的用途。
特别是,本发明涉及作为联合的选择性5-羟色胺(5-HT)再摄取抑制剂(SSRIs)和5-HT1A受体激动剂,如1-[4-(5-氰基吲哚-3-基)丁基]-4-(2-氨基甲酰基-苯并呋喃-5-基)-哌嗪或其生理上可接受的盐或3-{4-[4-(4-氰基-苯基)-哌嗪-1-基]-丁基}-1H-吲哚-5-腈或其生理上可接受的盐用于制备治疗与行为应激物有关的自我控制性创伤障碍和/或与行为应激物有关的强迫症的兽药的用途。
1-[4-(5-氰基吲哚-3-基)丁基]-4-(2-氨基甲酰基-苯并呋喃-5-基)-哌嗪,其生理上可接受的盐(US 5,532,241,第7栏,第30-58行)及制备它/它们的方法(US 5,532,241,实施例4)是从美国专利US 5,532,241获知的。此处所述化合物是作为联合的选择性5-羟色胺(5-HT)再摄取抑制剂(SSRI)和5-HT1A受体激动剂在专利中描述的。因此,公开了1-[4-(5-氰基吲哚-3-基)丁基]-4-(2-氨基甲酰基-苯并呋喃-5-基)-哌嗪及其生理上可接受的酸加成盐用于制备治疗抑郁症,包括严重抑郁症和心情忧郁症亚型,用于治疗焦虑症,用于治疗精神障碍如精神病,精神分裂症或分裂情感性障碍,用于治疗脑梗塞如中风和脑局部缺血,用于治疗CNS障碍如紧张,用于治疗高血压(例如,使用α-甲基多巴)治疗中出现的副作用和用于预防和治疗脑疾病(例如偏头痛)的用途。此外,还描述了在内分泌学和妇科学方面的用途,例如用于治疗肢端肥大症,性腺机能减退,继发性经闭,经前期综合征或不希望见到的产后泌乳。
3-{4-[4-(4-氰基-苯基)-哌嗪-1-基]-丁基}-1H-吲哚-5-腈,其生理上可接受的盐(EP 0 736 525,第3页,第5,26行,和第8页第28行-第9页第12行)及制备它/它们的方法(EP 0 736 525,实施例1)是从EP 0 736 525获知的。它们特别显示出对中枢神经系统的作用,特别是5-HT 1A-激动作用和5-HT-再摄取抑制作用。因此,它们适于治疗中枢神经系统障碍,如紧张状态,抑郁和/或精神病和高血压治疗中出现的副作用。此外,还描述了在内分泌学和妇科学方面的用途,例如用于治疗肢端肥大症,性腺机能减退,继发性闭经,经前期综合征或不希望的产后泌乳,且其还可用于预防和治疗脑疾病(例如偏头痛),特别是在老年病学方面,与某些麦角生物碱相似,并用于控制脑梗塞的后遗症(大脑卒中),如中风和脑局部出血。
本发明的目的是提供作为联合的选择性5-羟色胺(5-HT)再摄取抑制剂(SSRIs)和5-HT1A受体激动剂的化合物,特别是1-[4-(5-氰基吲哚-3-基)丁基]-4-(2-氨基甲酰基-苯并呋喃-5-基)-哌嗪及其生理上可接受的盐或3-{4-[4-(4-氰基-苯基)-哌嗪-1-基]-丁基}-1H-吲哚-5-腈或其生理上可接受的盐的新用途,特别是在兽药领域的用途。
人们已经发现作为联合的选择性5-羟色胺(5-HT)再摄取抑制剂(SSRIs)和5-HT1A受体激动剂,特别是1-[4-(5-氰基吲哚-3-基)丁基]-4-(2-氨基甲酰基-苯并呋喃-5-基)-哌嗪或其生理上可接受的盐或3-{4-[4-(4-氰基-苯基)-哌嗪-1-基]-丁基}-1H-吲哚-5-腈或其生理上可接受的盐在兽药方面还具有对抗与行为应激物有关的障碍的用途。
与行为应激物有关的障碍包括与行为应激物有关的自我控制性创伤障碍(也称为自伤行为),和与行为应激物有关的强迫症(例如,C.C.Pinney,The illustrated veterinary guide fordogs,cats,birds and exotic pets.(狗,猫,鸟和外来宠物的说明性兽医指南)。McGraw Hill,1992;U.A.Luescher,于:N.H.Dodman和L.Shuster(eds.):Psychopharmacology of AnimalBehavior(动物行为的精神药理学),Blackwell Science Inc.,Malden,1998,pp.203-221)。特别是,与行为应激物有关的自我控制性创伤障碍和与行为应激物有关的强迫症可导致动物的刻板行为,这是宠物主人,饲养员,动物管理员和兽医遇到的普遍问题。自我控制性创伤障碍的特征在于自伤行为,如狗的肢端舔皮炎(ALD),胁腹吮吸,旋转和捕寻尾巴(tail chaising),咬指甲及臀部的检查,猫的精神性脱毛(脱毛发),攻击尾部,用爪子抓脸部和感觉过敏或鸟啄羽毛(拔毛发癖)。
强迫症也可在其它种类的动物中见到,例如,动物园动物的反复或程式化溜蹄(ritualized pacing),马咬秣槽(cribbing),自残或迂回行进。
例如,高密度动物饲养的特征在于在有限的场地上饲养大量的动物。这种条件下饲养的动物要经历过度的紧张状态并发展成创伤性和强迫症,例如产肉饲养场中的猪咬栏杆或产蛋饲养场中的鸡啄羽毛(例如,M.Kiley-Worthinton,饲养场动物的行为问题(Behavioral problems of farm animals),Orial Press,Stockfields,1977;R.J.Young等,Appl.Anim.Behav.Sci.,1994,39:237-247)。
在兽医的工作实践中,这些障碍,特别是自我控制性创伤障碍,即狗的肢端舔皮炎,猫的精神性脱毛,笼养鸟啄羽毛,和马自残,咬秣槽及迂回行进是非常普遍的,这通常是宠物主人为什么请教兽医的原因(例如,R.R.Keiper,Anim.Behav.,1970,18:353-357;C.Davis,Vet.Clin.N Am.Sm.An.Pract.,1991,21:1281-1288;C.C.Pinney,狗,猫,鸟和外来宠物的说明性兽医指南。McGraw Hill,1992;D.J.Stein和N.H.Dodman,Comp.Psychiatr.,1994,35:275-285)。
肢端舔皮炎是一种特征在于狗过度舔并抓爪子的病。它可导致特异性皮炎;其它后遗症包括急性和慢性骨髓炎。肢端舔皮炎也称为舔肉芽肿,它可产生毛发缺损区,及损害的产生,按大小可从几厘米一直到肢体的全部表面,最终红肿发炎并溃烂,引起不适,疼痛,及严重情况下的残废。骨髓炎代表了骨组织的进行性化脓感染,并伴有骨破坏的症状,及骨中萎缩病灶的形成;在某些情况下还可形成死骨片和假关节。该疾病是在某一品种的大狗中见到的(特别是DobermanPinscher(德国种短毛猎犬),German Shephard(德国谢泼德狗),Great Danes(大丹麦狗),Golden Retriever(金毛猎犬),Labrador Retriever(拉布拉多猎狗),Irish Setter(以色列塞特种猎狗),和Weimaraner(魏玛狗)),且在某些品种的特殊种类中可能更普遍(例如,L.Veith,Canine Pract.,1986,14:15-22;J.J.Van Nes,J.Am.Vet.Med.Assoc.,1986,198:157-160;S.D.White,J.Am.Vet.Med.Assoc.,1990,202:1073-1076;B.A.Goldberger和J.L.Rapoport,J.Anim.Hosp.Assoc.,1990,27:179-182;U.A.Luescher等,Vet.Clin.N Am.Sm.Anim.Pract.,1991,21:401-413;K.Overall,J.Am.Vet.Assoc.,1994,205:1733-1741;U.A.Luescher,Vet.Intern.,1998,10:7-12)。
精神性脱毛可在猫中见到,过度脱毛导致斑秃(例如,U.A.Luescher等,Vet.Clin.N Am.Sm.Anim.Pract.,1991,21:401-413;J.W.S.Bradshaw等,J.Appl.An.Behav.Sci.,1997,52:373-379;J.Dehasse,Appl.An.Behav.,1997,52:365-371;L.S.Sawyer等,J.Am.Vet.Med.Assoc.,1999,214:71-74)。动物行为学家重点观察了与紧张状态有关的障碍。所有紧张均易导致精神性脱毛。
鸟啄羽毛可在许多鸟的种类中见到。与这种障碍有关的并发症包括严重的出血,感染,和低温。人们还获知,紧张状态和被禁闭在这种行为中起着重要的作用。这种疾病特别易于在非洲灰和Timneh灰,虎皮鹦鹉,玫瑰鹦鹉,neophemas及其它澳大利亚长尾小鹦鹉,美冠鹦鹉,锥尾鹦鹉,electus鹦鹉,吸蜜鹦鹉,多情鹦鹉,和金刚鹦鹉(例如,R.R.Keiper,Anim.Behav.,1970,18:353-357;D.Alderton,200多种鹦鹉的饲养重要参考,Salamander Books,1992;G.A.Gallerstein,完全鸟主人手册(The complete bird owner’shandbook),Macmillan,1994;C.Davis,Vet.Clin.N Am.Sm.An.Pract.,1991,21:1281-1288;F.Iglauer和R.Rasim,J.Sm.An.Pract.,1993,34:564-566;P.S:Brodnick等,J.Behav.Ther.Exp.Psychiatr.,1994,25:189-196;S.Blanchard,宠物鸟报告(Pet Bird Report),1995,23;S.V.Juarbe-Diaz,J.Am.Vet.Med.Assoc.,2000,1562-1564)中见到。
马的自残行为包括自咬(胁腹,四肢,外侧胸壁,胸部区域,尾部)和其它无法控制的激烈行为,通常包括绕圈旋转,突然拱背跃起,摩擦,有时用后肢踢同时在胁腹,肩部或胸部咬,和发声。在极端情况下,马会将其身体或头部猛烈地撞向墙壁或其它固体物体。单次发作可不间断地持续几分钟,一天之内还可能会反复发作达几小时。除了咬伤之外,最普遍的损伤是由旋转和踢造成的腿和足损伤。尽管自残可发生在两种性别及各种其它种类中,但最普遍发生于阿拉伯马,夸特马和美国标准饲养的种马中。(例如,A.F.Frazer,马的行为,CAB International,Oxon,1992;L.C.:Winskill等,Appl.An Behav Sci,1996,148:25-25)。
马咬秣槽的行为是一种最熟知的马厩恶癖。马咬物体,折曲它的颈部,用其牙齿向后拉,并吞咽空气。马咬秣槽不仅会损害房屋周围的物体,还会威胁它的生命。马咬秣槽可导致体重损耗,行为虚弱,气性急腹痛,和牙齿过度磨损(例如,N.H.Dodman等,Am.J.Vet.Res.,1987,48:311-319;M.Minero等,Proc.MeasuringBehav,1996)。
马的迂回行进行为是一种古怪的行为,马从一个前肢到另一个前肢摇摆很长一段时间。迂回行进通常发生在被关在马厩的马中(例如,A.F.Frazer,马的行为,CAB International,Oxon,1992)。
这些疾病的治疗是非常困难的,而且经常会抗任何疗法。
盐酸氯米帕明,一种具有5-羟色胺(5-HT)再摄取抑制性的三环抗抑郁药物已在狗(例如,P.A.Mertens和N.H.Dodman,Kleintierpraxis,1996,41:313-392;R.A.Eckstein和B.L.Hart,J.Am.An.Hosp.Assoc.,1996,32:225-230;R.A.Casey,Vet.Rec.,1998,142:587-588;A.L.Podberscek等,Vet.Rec.,1999,145:365-369),猫(例如,L.S.:Saxyer等,J.Am.Vet.Med.Assoc.,1999,214:71-74;K.Seksel和M.J.Lindeman,Aust.Vet.J.,1998,76:317-321),和鸟(例如,M.H.Grindlinger和E.Ramay,Proc.Assoc.Avian Vet.,1992)中使用。可选择地,选择性5-羟色胺(5-HT)再摄取抑制剂(SSRIs),如氟西汀可用于包括马(例如,K.L.Overall,Can.Pract.,1996,21:20-24;P.A.Mertens,ESVCE Newsletter,1997,3:n°4/5;H.G.Nurnberg等,Biol.Psychiatr.,1997,41:226-229;D.Wynchank和M.Berk,Depress.Anxiety,1998,8:21-23;J.Romatowski,Feline Pract.,1998,26:14-15)在内的种类。最终,还报道了可将多巴胺拮抗剂,如氟哌啶醇有效地用于狗,猫,鸟和马(例如,F.Iglauer和R.Rasim,J.Sm.An.Pract.,1993,34:564-566;H.G.Nurnberg等,Biol.Psychiatr.,1997,41:226-229;U.A.Luescher,in:N.H.Dodman和L.Shuster(eds.):动物行为的精神药理学,BlackwellScience Inc.,Malden,1998,pp.203-221)。
虽然5-羟色胺5-HT1A受体激动剂还没有被确定为动物的药理学疗法,但已经建议将5-HT1A受体激动剂丁螺环酮用于狗和猫(B.L.Hart等,J.Am.Vet.Med.Assoc.,1993,203:254-258;K.L.Overall,J.Am.Vet.Med.Assoc.,1994,205:694-696;W.Jochle,Tierrztl.Prax.,1998,26:410-421)。但人们很长时间以来就已经知道5-HT1A受体激动剂可减轻动物(例如,J.E.Barrett和K.E.Vanover,精神药理学,1993,112:1-12;G.Griebel,Pharmac.Ther.,1995,65:319-395;F.G.Graeff等,Pharmacol.Biochem.Behav.,1996,54:129-141)和人(例如,J.P.Feighner等,J.Clin.Psychiatr.,1982,43:103-108;A.F.Jacobson等,药物疗法,1985,5:290-296;J.J.Sramek等,Depress.Anxiety,1999,9:131-134)的紧张状态并缓解焦虑。此外,对于人类强迫观念与行为的障碍而言,单独使用5-HT1A受体激动剂也是有效的(J.P.Apter和L.A.Allen,J.Clin.Psychopharmacol.,1999,19:86-93),特别是可增加SSRIs的作用(P.J.Markovitz等,Am.J.Psychiatr.,1990,147:798-800),人类强迫观念与行为的障碍在各个方面(例如,拔毛发癖,咬甲癖,强迫性检查)均与动物的自我控制性创伤障碍和强迫症相似(例如,E.Yadin等,Pharmacol.Biochem.Behav.,1991,40:311-315;J.L.Rapoport等,Arch.Gen.Psychiatr.,1992,49:517-521;P.S.Bordnick等,J.Behav.Ther.Exp.Psychiatr.,1994,25:189-196;D.J.Stein和N.H.Dodman,Comp.Psychiatr.,1994,35:275-285;H.G.Nurnberg等,Biol.Psychiatr.,1997,41:226-229;H.Szechtman等,Behav.Neurosci.,1998,112:1475-1485,Pol.J.Pharmacol.,1999,51:55-61)。因此,选择性5-羟色胺(5-HT)再摄取抑制性与5-HT1A受体激动性的结合代表了一种比单独使用SSRIs或5-HT1A受体激动剂更优的方法,可用于治疗自我控制性创伤障碍和强迫症。
因此,本发明涉及作为联合的选择性5-羟色胺(5-HT)再摄取抑制剂(SSRIs)和5-HT1A受体激动剂的化合物,特别是1-[4-(5-氰基吲哚-3-基)丁基]-4-(2-氨基甲酰基-苯并呋喃-5-基)-哌嗪或其生理上可接受的盐或3-{4-[4-(4-氰基-苯基)-哌嗪-1-基]-丁基}-1H-吲哚-5-腈或其生理上可接受的盐用于制备治疗自我控制性创伤障碍,包括狗肢端舔皮炎,猫精神性脱毛和鸟啄羽毛,和/或强迫症的兽药的用途。
因此,本发明涉及1-[4-(5-氰基吲哚-3-基)丁基]-4-(2-氨基甲酰基-苯并呋喃-5-基)-哌嗪或其生理上可接受的盐用于制备治疗与行为应激物有关的障碍的兽药的用途。
本发明还涉及3-{4-[4-(4-氰基-苯基)-哌嗪-1-基]-丁基}-1H-吲哚-5-腈或其生理上可接受的盐用于制备治疗与行为应激物有关的障碍的兽药的用途。
优选的1-[4-(5-氰基吲哚-3-基)丁基]-4-(2-氨基甲酰基-苯并呋喃-5-基)-哌嗪的盐是1-[4-(5-氰基吲哚-3-基)丁基]-4-(2-氨基甲酰基-苯并呋喃-5-基)-哌嗪的盐酸盐。
因此,本发明涉及用于制备治疗与行为应激物有关的障碍的兽药的用途,其中1-[4-(5-氰基吲哚-3-基)丁基]-4-(2-氨基甲酰基-苯并呋喃-5-基)-哌嗪药理上可接受的盐是1-[4-(5-氰基吲哚-3-基)丁基]-4-(2-氨基甲酰基-苯并呋喃-5-基)-哌嗪的盐酸盐。
优选的3-{4-[4-(4-氰基-苯基)-哌嗪-1-基]-丁基}-1H-吲哚-5-腈的盐是3-{4-[4-(4-氰基-苯基)-哌嗪-1-基]-丁基}-1H-吲哚-5-腈的盐酸盐。
因此,本发明涉及用于制备治疗与行为应激物有关的障碍的兽药的用途,其中3-{4-[4-(4-氰基-苯基)-哌嗪-1-基]-丁基}-1H-吲哚-5-腈药理上可接受的盐是3-{4-[4-(4-氰基-苯基)-哌嗪-1-基]-丁基}-1H-吲哚-5-腈的盐酸盐。
此外,本发明涉及用于治疗与行为应激物有关的障碍的药物组合物,其中所述药物组合物含有作为联合的选择性5-羟色胺(5-HT)再摄取抑制剂(SSRI)和5-HT1A受体激动剂的化合物,特别是1-[4-(5-氰基吲哚-3-基)丁基]-4-(2-氨基甲酰基-苯并呋喃-5-基)-哌嗪或其生理上可接受的盐或3-{4-[4-(4-氰基-苯基)-哌嗪-1-基]-丁基}-1H-吲哚-5-腈或其生理上可接受的盐,和至少一种固体,液体或半液体的赋形剂或添加剂。
因此,本发明提供一种用于兽药的,治疗与行为应激物有关的障碍的药物制剂,其特征在于它至少含有1-[4-(5-氰基吲哚-3-基)丁基]-4-(2-氨基甲酰基-苯并呋喃-5-基)-哌嗪和/或其一种药学上可接受的盐及至少一种辅助物质。
因此,本发明提供一种用于兽药的,治疗与行为应激物有关的障碍的药物制剂,其特征在于它至少含有3-{4-[4-(4-氰基-苯基)-哌嗪-1-基]-丁基}-1H-吲哚-5-腈和/或其一种药学上可接受的盐及至少一种辅助物质。
适宜的赋形剂是有机或无机物质,其适于肠内(例如,口服),肠胃外或局部给药,而且它不与活性化合物反应,例如水,植物油,苯甲醇,烷撑二醇,聚乙二醇,甘油三乙酸酯,明胶,碳水化合物如乳糖或淀粉,硬脂酸镁,滑石粉,凡士林。具体地说,用于口服给药的形式是片剂,丸剂,糖衣片,胶囊剂,粉剂,颗粒剂,糖浆剂,液体或滴剂,用于直肠给药的形式是栓剂,用于肠胃外给药的形式是溶剂,优选油溶液或水溶液,此外还有混悬液,乳状液或植入物,用于局部给药的形式是透皮橡皮膏剂,软膏剂,乳膏或粉剂。此外还可将所述活性化合物冷冻干燥,所得冷冻干燥物用于制备例如注射用产品。上述制剂可以是灭菌形式和/或含有助剂如助流剂,防腐剂,稳定剂和/或湿润剂,乳化剂,调节渗透压的盐,缓冲物质,着色剂,调味剂和/或其它活性成分,例如一种或多种维生素。
本发明化合物1-[4-(5-氰基吲哚-3-基)丁基]-4-(2-氨基甲酰基-苯并呋喃-5-基)-哌嗪及其药学上可接受的盐或3-{4-[4-(4-氰基-苯基)-哌嗪-1-基]-丁基}-1H-吲哚-5-腈及其药学上可接受的盐优选可按照与其它已知市售的,用于治疗与行为应激物有关障碍的兽药相似的方式给药。一个单位剂量通常含有0.1-300mg,优选约0.1(用于小鸟)-100mg(用于大狗),特别是0.1,0.5,1,5,10,30,50,100,200,和300mg。所述组合物可一天给药一次,或给药几次,例如一天给药2,3或4次。每日剂量优选约1-10mg/kg体重。然而,每个受体动物的特定剂量不仅取决于种类,而且还取决于各种因素,例如所用特定化合物的活性,年龄,体重,一般的健康状况,性别,饮食,给药时间和途径,排泄率,药用物质的结合和该疗法所治疗的具体疾病的严重程度。口服给药是优选的;适宜的剂量通常可毫不费力地与食物混合,但也可使用经口给药途径(例如,肌肉内或透皮)。
为了证实本发明化合物的功效,描述了下列临床研究:
实施例1:
本研究的目的是评估所述化合物治疗狗肢端舔皮炎(ALD)的功效,该研究是涉及到兽医医师的多中心、安慰剂-对照研究(J.L.Rapoport等,Arch.Gen..Psychiatr.,1992,49:517-521;D.Wynchank和M.Berk,Depress.Anxiety,1998,8:21-23;A.L.Podberscek等,Vet.Rec.,1999,145:365-369)。
每天两次,以2mg/kg的剂量,用化合物或安慰剂治疗40只患ALD的狗,8周。如果需要,可根据临床反应调整剂量。由主人每周评估损害的外观和舔的行为,并由兽医评估治疗前和治疗后的损害。
实施例2:
本研究的目的是评估所述化合物治疗猫精神性脱毛的功效,该研究是涉及到兽医医师的多中心、安慰剂-对照研究(根据K.Seksel和M.J.Lindeman,Aust.Vet.J.,1998,76:317-321)。
每天两次,以1mg/kg的起始剂量,用化合物或安慰剂治疗28只精神性脱毛的猫,8周。如果需要,可根据临床反应调整剂量。由主人每周评估损害的外观和大小,并由兽医评估治疗前和治疗后的损害。
实施例3:
本研究的目的是评估所述化合物治疗鸟啄羽毛的功效,该研究是涉及到兽医医师的多中心、安慰剂-对照研究(根据P.A.Mertens,ESVCE Newsletter,1997,n. 4/5)。
每天三次,以3mg/kg的剂量,用化合物或安慰剂治疗24只啄羽毛的鸟,至少4周,直到8周。如果需要,可根据临床反应调整剂量。由主人评估羽毛减少所造成损害的外观和大小,并由兽医评估治疗前和治疗后的损害(4周和8周)。
Claims (3)
1.作为联合的选择性5-羟色胺再摄取抑制剂和5-HT1A受体激动剂的化合物用于制备治疗与行为应激物有关的障碍的兽药的用途,其中所述作为联合的选择性5-羟色胺再摄取抑制剂和5-HT1A受体激动剂的化合物选自1-[4-(5-氰基吲哚-3-基)丁基]-4-(2-氨基甲酰基-苯并呋喃-5-基)-哌嗪或其生理上可接受的盐或3-{4-[4-(4-氰基-苯基)-哌嗪-1-基]-丁基}-1H-吲哚-5-腈或其生理上可接受的盐。
2.根据权利要求1所述的用途,其中所述1-[4-(5-氰基吲哚-3-基)丁基]-4-(2-氨基甲酰基-苯并呋喃-5-基)-哌嗪的生理上可接受的盐是1-[4-(5-氰基吲哚-3-基)丁基]-4-(2-氨基甲酰基-苯并呋喃-5-基)-哌嗪的盐酸盐。
3.根据权利要求1所述的用途,其中所述3-{4-[4-(4-氰基-苯基)-哌嗪-1-基]-丁基}-1H-吲哚-5-腈的生理上可接受的盐是3-{4-[4-(4-氰基-苯基)-哌嗪-1-基]-丁基}-1H-吲哚-5-腈的盐酸盐。
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