概述
氟哌啶醇属于丁酰苯类抗精神病药物,又名氟哌丁苯、氟哌醇或卤吡醇。它主要用于治疗急性和慢性精神分裂症、躁狂症以及反应性精神病等疾病。此外,对伴有兴奋、躁动、幻觉和妄想等症状的重症精神病也有显著疗效,尤其是急性青光眼及有攻击行为的偏执型精神分裂症患者。由于其心血管系统不良反应较少,也被用于治疗脑器质性精神障碍、焦虑性神经症及老年性精神障碍。
药理作用
氟哌啶醇的药理作用与酚噻嗪类抗精神病药物类似,通过阻断大脑内的多巴胺受体,抑制多巴胺神经元的功能,并加速和增多脑内多巴胺的转化。这导致其具有良好的抗幻觉妄想及抗兴奋躁动效果;同时,该药对锥体外系多巴胺的作用较强,镇吐作用显著但镇静、阻断肾上腺素受体及胆碱受体作用较弱,需要与其他药物联合使用。
吸收与代谢
氟哌啶醇口服后约有70%被吸收,并具有较高的血浆蛋白结合率。通常在3至6小时达到峰值血药浓度。该药物的半衰期约为21小时,在肝脏内代谢并随尿液排出,少量会分泌入乳汁及通过胆汁排泄。
作用机制
氟哌啶醇通过阻断脑内的多巴胺受体起作用,抑制多巴胺神经元的功能,并加速多巴胺的转化。此外,还能阻断植物神经系统中的α-肾上腺素受体,产生相应的生理影响。
药动学
口服后有70%被吸收,一般在3至6小时或肌内注射10至20分钟后达到峰值血药浓度。药物主要分布在肝脏,少量分布于骨骼肌,并可通过血脑屏障进入大脑。约40%的药物会在5天内通过尿液排出,其中1%为原形药物。
不良反应
氟哌啶醇最常见的副作用是锥体外系症状,如静坐不能、运动障碍、震颤和肌张力异常等。儿童、老年人及有脑病变者更容易出现这些症状。长期大量使用可能导致迟发性运动障碍。少数患者可能出现口干、视力模糊、头晕、乏力、便秘、出汗、抑郁反应、过敏性皮疹、粒细胞减少以及恶性综合征等症状,罕见情况下还会引起高热和心电图异常。
过量与禁忌
过量使用氟哌啶醇可能导致角弓反张、扭转痉挛及抽搐等急性脑病症状。发现超剂量时,可适当应用抗胆碱药物,通常3至7天后会缓解。禁忌症包括心功能不全、基底神经节病变以及孕妇和哺乳期妇女。
氟哌啶醇是丁酰苯类的抗精神病药,结构中含手性碳原子,右旋体活性更强。该药物为白色或类白色的结晶粉末,熔点在148至149.4℃之间,能溶于氯仿、甲醇和丙酮等有机溶剂,在水中的溶解度较低。
用途
氟哌啶醇作为丁酰苯类抗精神病药中最常用的一种药物,被纳入《国家基本药物目录》。主要用于治疗精神分裂症及其他伴有幻觉、妄想及兴奋等症状的疾病。对于急性和慢性精神分裂症患者的躁狂和幻觉症状具有显著疗效,但对抑郁和淡漠无效。
生产方法
氟哌啶醇可通过4-对氯苯-4-羟基哌(见09670)与γ-氯代对氟苯丁酮缩合制得。中间体γ-氯代氟苯丁酮则由氟苯、γ-丁内酯和氯化亚砜合成(见09060)。
中文名称 | 英文名称 | CAS号 | 化学式 | 分子量 |
---|---|---|---|---|
4-[4-(4-氯苯基)-4羟基-1-哌啶基]-1-(4-氯苯基)-1-丁酮 | 1-(4-chlorophenyl)-4-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)butan-1-one | 59995-68-5 | C21H23Cl2NO2 | 392.325 |
—— | 4-(4-chlorophenyl)-1-(4-(4-fluorophenyl)butyl)piperidin-4-ol | 164668-08-0 | C21H25ClFNO | 361.887 |
还原氟哌啶醇 | reduced haloperidol | 34104-67-1 | C21H25ClFNO2 | 377.886 |
4-(4-氯苯基)-4-羟基哌啶 | 4-(4-Chlorophenyl)-4-hydroxypiperidine | 39512-49-7 | C11H14ClNO | 211.691 |
4-(4-氯苯基)-1-[3-[2-(4-氟苯基)-1,3-二氧戊环-2-基]丙基]哌啶-4-醇 | 4-<4-(4-chlorophenyl)-4-hydroxypiperidino>-1,1-ethylenedioxy-1-(4-fluorophenyl)butane | 56660-99-2 | C23H27ClFNO3 | 419.924 |
1-苄基-4-(4-氯苯基)-4-哌啶醇 | N-benzyl-4-(4-chlorophenyl)-4-hydroxypiperidin | 56108-25-9 | C18H20ClNO | 301.816 |
中文名称 | 英文名称 | CAS号 | 化学式 | 分子量 |
---|---|---|---|---|
—— | <18F>haloperidol | —— | C21H23ClFNO2 | 374.872 |
顺式/反式-氟哌啶醇N-氧化物 | Haloperidol N-oxide | 148406-51-3 | C21H23ClFNO3 | 391.87 |
—— | 4-(4-chlorophenyl)-1-(4-(4-fluorophenyl)butyl)piperidin-4-ol | 164668-08-0 | C21H25ClFNO | 361.887 |
—— | 4-<4-hydroxy-4-(4-aminophenyl)piperidinyl>-1-(4-fluorophenyl)butanone | 114361-10-3 | C21H25FN2O2 | 356.44 |
还原氟哌啶醇 | reduced haloperidol | 34104-67-1 | C21H25ClFNO2 | 377.886 |
—— | (R)-(+)-4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-hydroxybutyl]piperidin-4-ol | 136271-60-8 | C21H25ClFNO2 | 377.886 |
—— | Haloperidol TMS derivative | —— | C24H31ClFNO2Si | 448.053 |
—— | 4-<4-(4-Chlorophenyl)-4-hydroxypiperidino>-4'-<<2-(dimethylamino)ethyl>amino>butyrophenone | —— | C25H34ClN3O2 | 444.017 |
—— | 4-<4-(4-Chlorophenyl)-4-hydroxypiperidino>-4'-<<3-(dimethylamino)propyl>amino>butyrophenone | —— | C26H36ClN3O2 | 458.044 |
—— | 1-[4-(p-fluorophenyl)-4-oxo-2-butenyl]-4-(p-chlorophenyl)-4-hydroxypiperidine | —— | C21H21ClFNO2 | 373.855 |
—— | 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl acetate | 115250-18-5 | C23H25ClFNO3 | 417.908 |
—— | 4-<4-<4-(Dibutylamino)phenyl>-4-hydroxypiperidino>-4'-fluorobutyrophenone | —— | C29H41FN2O2 | 468.655 |
—— | 4-<4-<3-(Butylamino)phenyl>-4-hydroxypiperidino>-4'-fluorobutyrophenone | —— | C25H33FN2O2 | 412.548 |
—— | 4-<4-<4-(Cyclohexylamino)phenyl>-4-hydroxypiperidino>-4'-fluorobutyrophenone | —— | C27H35FN2O2 | 438.586 |
—— | 4-<4-(4-Chlorophenyl)-4-hydroxypiperidino>-4'-(dibutylamino)butyrophenone | —— | C29H41ClN2O2 | 485.11 |
—— | 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl propionate | 109765-78-8 | C24H27ClFNO3 | 431.935 |
—— | 4-<4-(4-Chlorophenyl)-4-hydroxypiperidino>-4'-piperidinobutyrophenone | —— | C26H33ClN2O2 | 441.013 |
—— | 4-<4-(4-Chlorophenyl)-4-hydroxypiperidino>-4'-(cyclohexylamino)butyrophenone | —— | C27H35ClN2O2 | 455.04 |
—— | 4-<4-<3-(Diethylamino)phenyl>-4-hydroxypiperidino>-4'-fluorobutyrophenone | —— | C25H33FN2O2 | 412.548 |
—— | [4-(4-Chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl] 3-aminopropanoate | 853994-08-8 | C24H28ClFN2O3 | 446.949 |
—— | 4-<4-(4-Chlorophenyl)-4-hydroxypiperidino>-4'-<(N,N-dimethyl-N'-ethyl)amino>butyrophenone | —— | C27H38ClN3O2 | 472.071 |
—— | 1-(4-fluorophenyl)-4-(4-hydroxy-4-(4-((3-(trifluoromethyl)phenyl)amino)phenyl)piperidin-1-yl)butan-1-one | 1612891-27-6 | C28H28F4N2O2 | 500.536 |
—— | bis{4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl} succinate | 1622913-78-3 | C46H48Cl2F2N2O6 | 833.8 |
—— | bis{4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4yl} pentanedioate | 1622913-79-4 | C47H50Cl2F2N2O6 | 847.827 |
—— | bis{4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl} pimelate | 1622913-81-8 | C49H54Cl2F2N2O6 | 875.88 |
—— | bis{4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl} hexanedioate | 1622913-80-7 | C48H52Cl2F2N2O6 | 861.853 |
氟哌啶醇辛酸酯 | haloperidol octanoate | 1134807-34-3 | C29H37ClFNO3 | 502.069 |
—— | bis{4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidine-4-yl} dodecanedioate | 1622913-85-2 | C54H64Cl2F2N2O6 | 946.015 |
—— | bis{4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl} suberate | 1622913-82-9 | C50H56Cl2F2N2O6 | 889.907 |
—— | bis{4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl} azelaate | 1622913-83-0 | C51H58Cl2F2N2O6 | 903.934 |
—— | bis{4-(4-chlorophenyl)-1-[4(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl} sebacate | 1622913-84-1 | C52H60Cl2F2N2O6 | 917.961 |
—— | bis{4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl} tetradecanedioate | 1622913-86-3 | C56H68Cl2F2N2O6 | 974.069 |
—— | bis{4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl} hexadecanedioate | 1622913-87-4 | C58H72Cl2F2N2O6 | 1002.12 |
—— | bis{4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl} octadecanedioate | 1622913-88-5 | C60H76Cl2F2N2O6 | 1030.18 |
4-(4-氯苯基)-1-[4-(4-氟苯基)-4-氧丁基]-4-哌啶癸酸盐 | Haloperidol decanoate | 74050-97-8 | C31H41ClFNO3 | 530.123 |
—— | bis{4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl} icosanedioate | 1622913-89-6 | C62H80Cl2F2N2O6 | 1058.23 |
—— | bis{4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl} docosanedioate | 1622913-90-9 | C64H84Cl2F2N2O6 | 1086.28 |
—— | benzoic acid haloperidol ester | —— | C28H27ClFNO3 | 479.979 |
—— | 4-<4-<3-(Cyclohexylamino)phenyl>-4-hydroxypiperidino>-4'-fluorobutyrophenone | —— | C27H35FN2O2 | 438.586 |
—— | 4-[4-(4-Chloro-phenyl)-4-hydroxy-piperidin-1-yl]-1-(4-fluoro-phenyl)-2-phenylselanyl-butan-1-one | 153535-46-7 | C27H27ClFNO2Se | 530.928 |
—— | 4-<4-<3-(Dibutylamino)phenyl>-4-hydroxypiperidino>-4'-fluorobutyrophenone | —— | C29H41FN2O2 | 468.655 |
—— | 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl 4-methylbenzoate | 1622913-91-0 | C29H29ClFNO3 | 494.006 |
—— | (E)-4-[4-(4-Chloro-phenyl)-4-hydroxy-1-oxy-piperidin-1-yl]-1-(4-fluoro-phenyl)-but-2-en-1-one | —— | C21H21ClFNO3 | 389.854 |
—— | 1-(n-Butoxyphenyl)-4-<4-(4-chlorophenyl)-4-hydroxypiperidino>-n-butyl alcohol | —— | C25H34ClNO3 | 432.003 |
—— | [4-(4-Chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl] 3-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate | 853994-07-7 | C29H36ClFN2O5 | 547.067 |
五氟利多 | penfluridol | 26864-56-2 | C28H27ClF5NO | 523.973 |
—— | 4-<4-<3-(Dibutylamino)phenyl>-4-hydroxypiperidino>-4'-(cyclohexylamino)butyrophenone | —— | C35H53N3O2 | 547.825 |
HPTP; 4-[4-(4-氯苯基)-3,6-二氢-1(2H)-吡啶基]-1-(4-氟苯基)-1-丁酮 | 4-(4-chlorophenyl)-1-<4-(4-fluorophenyl)-4-oxobutyl>-1,2,3,6-tetrahydopyridine | 52669-92-8 | C21H21ClFNO | 357.855 |
—— | 4-(4-chlorophenyl)-1-{2-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]ethyl}piperidin-4-ol | —— | C22H23ClFN3O | 399.896 |