氟哌啶醇在增强脑膜与依托啡结合的同时加强针刺镇痛

用氚标记依托啡［３Ｈ］－ｅｔｏｒｐｈｉｎｅ与兔脑匀浆蛋白作受体结合试验,Ｓｃａｔｃｈａｒｄ分析的结果显示兔脑内的阿片受体有高低两种亲和力结合,对照组兔脑高亲和力解离常数Ｋｄｌ为２．５７±０．３３ｎｍｏｌ／Ｌ,氟哌啶醇（ｈａｌｏｐｅｒｉｄｏｌ,ｈａｌ）或针刺引起镇痛时,Ｋｄｌ值分别降至１．４４±０．０３ｎｍｏｌ／Ｌ和１．５３±０．０５ｎｍｏｌ／Ｌ（Ｐ＜０．０５）;当ｈａｌ和针刺合用进一步加强镇痛时,Ｋｄｌ值进一步降至１．２５±０．３３ｎｍｏｌ／Ｌ（Ｐ＜０．０１）,提示在ｈａｌ加强针刺镇痛时兔脑阿片受体的亲和力提高。兔脑同［３Ｈ］－ｅｔｏｒｐｈｉｎｅ作体外受体结合放射自显影,结果显示ｈａｌ加强针刺镇痛时,尾核、视前外侧区、丘脑室旁核、中央正中核、丘脑背外侧核和中脑导水管周围灰质等脑区的阿片受体结合密度均有显著提高。上述结果提示,多巴胺受体拮抗剂ｈａｌ加强针刺镇痛的机制之一,可能是由于产生了脑内阿片受体的上行调节。     

奥氮平合并丙戊酸钠治疗难治性精神分裂症的对照分析

目的:探讨奥氮平联合丙戊酸钠治疗难治性精神分裂症的疗效.方法:将80例精神分裂症患者按随机数字法分为联合用药组(奥氮平+丙戊酸钠组)40例和单用药组(奥氮平组)40例.联合用药组服用奥氮平起始量为10 mg/d,1周末加至20 mg/d,同时使用丙戊酸钠起始量为600 mg/d,最大剂量1200 mg/d.单药组服用奥氮平,用法同联合用药组.2组均为8周1疗程.对2组采用阳性与阴性症状量表(PANSS)评定疗效,采用不良反应量表(TESS)评定治疗中不良反应.于治疗2周末、4周末、8周末测定奥氮平血药浓度.结果:第8周末,两组PANSS评分较治疗前均下降(P均＜0.05),联合用药组较单用药组联合用药组PANSS(P＜0.001)、阳性症状(P＜0.001)、阴性症状(P＜0.05)均明显改善,两组不良反应差异无统计学意义(P＞0.05).结论:奥氮平联合丙戊酸钠治疗难治性精神分裂症可提高疗效且安全性高.     

帕利哌酮和奥氮平在急性期精神分裂症的随机对照研究

目的:研究帕利哌酮治疗急性期精神分裂症的疗效和安全性.方法:94例符合国际疾病分类第10版(ICD-10)诊断标准的精神分裂症急性期患者随机分为帕利哌酮组(N=45)和奥氮平组(N=49),采用简明精神病量表(the Brief Psychiatric Rating Scale,BPRS)、阳性和阴性症状量表(the Positive and Negative Syndrome Scale,PANSS)及个人和社会功能量表(Personal and Social Performance Scale,PSP)评定疗效,采用治疗中需处理的不良反应症状量表(Treatment Emergent Symptoms Scale,TESS)评定安全性.结果:两组治疗后BPRS和PANSS评分均低于治疗前,帕利哌酮组BPRS评分(23.15± 4.12)vs.(47.45± 3.87),PANSS评分(51.06± 6.87)vs.(87.96± 4.16),P＜0.05;奥氮平组BPRS评分(26.96± 4.30)vs.(45.11±3.18),PANSS评分(58.42± 5.72)vs.(84.71± 10.31),P＜0.05;治疗后,帕利哌酮组BPRS、PANSS评分低于奥氮平组,但差异无统计学意义(P＞o.05).两组治疗后PSP评分均优于治疗前,且帕利哌酮组效果较奥氮平组效果更好(P＜0.05).两组TESS评分在治疗后差异无统计学意义(P＞0.05).结论:帕利哌酮治疗急性期精神分裂症疗效,安全性较高,是一种值得借鉴的策略.     

氟哌啶醇和（R—）—NPA抑制C6神经胶质瘤细胞的钾电流

本工作用全细胞膜片箝方法,观察了氟啶醇（ｈａｌｏｐｅｒｉｄｏｌ以下简称ＨＡＬＯ）和Ｒ（－）－Ｐｒｏｐｙｌｎｏｒａｐｏｍｏｒｐｈｉｎｅ（以下简称ＮＰＡ）对Ｃ６神经胶质瘤细胞（Ｃ６ｇｌｉｏｍａｃｅｌｌｓ）的电压依赖性钾电流的作用,并初步分析了它们的作用机制。结果表明,ＨＡＬＯ和ＮＰＡ都能抑制Ｃ６细胞的Ｋ＾＋Ｊ电流中的慢成分,而对快成分的作用有所不同。它们的抑制作用不是由多巴胺Ｄ２受体介导的,也不是通过     

奥氮平联合重复经颅磁刺激或改良电休克治疗精神分裂症的疗效分析

目的:比较抗精神病药物奥氮平联合复经颅磁刺激(rTMS)或改良电休克(MECT)治疗精神分裂症的疗效。方法:将84例精神分裂症患者随机分为rTMS组(42例)与MECT组(42例),两组分别在奥氮平的基础上联合MECT或rTMS进行治疗。在治疗2、4、8周末后,采用阳性症状和阴性症状量表PANSS、治疗时出现症状量表TESS评估临床治疗效果及不良反应,同时采用修订韦氏记忆量表(WMS-RC)和威斯康星卡片分类测验(WCST)评定认知功能。结果:治疗后,两组总有效率比较无统计学差异(P0.05)。两组治疗后PANSS总分、阳性症状、阴性症状和一般病理分值均显著低于治疗前(P0.05,P0.01),但组间比较无统计学差异(P0.05)。两组TESS评分及不良反应的发生情况比较无统计学差异(P0.05)。与治疗前相比,两组患者治疗后认知功能均显著改善(P0.05,P0.01),且rTMS联合组在改善患者记忆功能、执行能力方面效果优于MTCT组(P0.05)。结论:奥氮平联合MECT或rTMS对精神分裂症状的疗效相当,但联合rTMS可更显著改善患者的认知功能。     

右美托咪定和丙泊酚用于电休克治疗联合奥氮平治疗精神分裂症疗效的影响

摘要 目的：探究精神分裂症患者联用奥氮平与电休克治疗的可行性,并分析电休克治疗前应用右美托咪定和丙泊酚对患者应激反应的影响。方法：选择2019年4月至2021年4月在我院接受治疗的120例精神分裂症患者为研究对象,将其按照随机数字表法区分为A组、B组和C组（每组各40例患者）,A组患者单纯接受奥氮平治疗,B组患者在A组基础上加用电休克治疗（术前使用丙泊酚麻醉）,C组在B组电休克治疗基础上加用右美托咪定麻醉,就A组和B组患者治疗前后的PANSS评分及治疗效果进行比较,就B组和C组患者血流动力学指标、电休克治疗指标以及不良反应发生率进行比较。结果：（1）治疗前两组患者PANSS量表中阳性症状、阴性症状、一般精神病理及总分组间无差异（P>0.05）,治疗6周后B组患者阳性症状、阴性症状、一般精神病理及总分均明显低于A组（P<0.05）;（2）麻醉前（T0）时两组患者的HR、MAP组间比较无差异（P>0.05）,而在麻醉给药10 min（T1）和电击后5 min（T2）时,C组患者的HR与MAP均低于B组（P<0.05）;（3）B组与C组患者电休克治疗的相关指标诸如苏醒时间、自主呼吸恢复时间以及能量抑制指数上组间无差异（P>0.05）;（4）B组患者呃逆、躁动、头痛等不良反应总发生率为32.50 %（13/40）高于C组患者上述不良反应总发生率5.00 %（2/40）（P<0.05）。结论：电休克治疗联合奥氮平对精神分裂症具有较好的治疗效果,术前若能够联用右美托咪定和丙泊酚进行麻醉,将显著改善患者应激症状,降低术后各类并发症发生率。     

奥氮平联合氟西汀治疗对抑郁症患者血清NE水平以及抑郁情绪影响的临床研究

摘要 目的：研究奥氮平联合氟西汀治疗抑郁症患者的临床疗效,并探讨联合治疗对抑郁症患者血清去甲肾上腺素（Norepinephrine,NE）和抑郁情绪的影响。方法：纳入2018年6月到2020年5月在我院接受治疗的抑郁症患者56例,随机数表法将其分为对照组和研究组两组。对照组患者接受氟西汀治疗,而研究组患者接受奥氮平联合氟西汀治疗,两组患者均治疗8周。比较两组患者年龄、性别、身高、BMI以及病程等一般资料,并比较两组患者临床治疗疗效、治疗期间不良反应发生率、治疗前后血清NE水平。用汉密顿抑郁量表(Hamilton Rating Scale for Depression,HAMD)和抑郁自评量表（Self-Rating Depression Scale,SDS）评估两组患者抑郁情绪。结果：两组患者性别、年龄、身高、BMI、病程以及合并症等一般情况均显示无显著差异（P>0.05）。研究组治疗总有效率（92.86%）显著高于对照组（64.29%）总治疗有效率（P<0.05）,但研究组患者治疗期间不良发生率（32.14%）与对照组（28.57%）比较无显著差异（P>0.05）。治疗后,两组患者血清NE水平均较治疗前显著升高（P<0.05）,并且研究组患者治疗后血清NE水平均显著高于对照组患者（P<0.05）;两组患者血清HAMD和SDS评分均较治疗前显著降低（P<0.05）,并且研究组患者治疗后HAMD和SDS评分均显著低于对照组患者（P<0.05）。结论：奥氮平联合氟西汀治疗抑郁症患者安全有效,不良反应发生率较低,可有效升高抑郁症患者血清NE水平,而改善患者抑郁情绪。     

阿立哌唑与利培酮治疗难治性精神分裂症的临床疗效对比

目的:研究对比阿立哌唑与利培酮治疗难治性精神分裂症(简称难治性精分症)的临床疗效。方法:选择2012年6月至2015年5月在我院接受治疗的难治性精分症患者108例进行研究。根据数字法随机将患者分成观察组及对照组各54例,观察组给予阿立哌唑治疗,对照组给予利培酮治疗,8周后对比两组治疗后的总体疗效,不良反应情况,以及不同时期阴性与阳性症状量表(PANSS)评分值。结果:观察组治疗后的总有效率92.59%,显著高于照组的77.78%(P0.05)。两组治疗1周后~治疗8周后的阳性症状、阴性症状、一般病理及PANSS总分均分别显著低于治疗前的水平(P0.05),且观察组治疗1周后~治疗8周后的阴性症状及PANSS总分均分别显著低于对照组(P0.05)。观察组治疗后的不良反应总发生率为33.33%,显著低于对照组的64.81%(P0.05)。结论:阿立哌唑较利培酮治疗难治性精分症可获得更好的疗效及安全性,建议可在临床进一步研究和推广应用。     

奥氮平与氯氮平治疗急性期精神病的对照研究

目的:探讨奥氮平与氯氮平在治疗急性期精神病的疗效比较。方法:根据治疗方法不同,将符合条件的100例急性期精神病患者随机分为实验组与对照组,两组各50例,其中实验组采用奥氮平治疗,对照组采用氯氮平治疗,采用BPRS评分对治疗2周后的精神症状进行评价,同时对两组的总显效率进行比较。结果:治疗后实验组患者的BPRS评分较对照组明显降低,差异显著(P0.05),另外实验组的2周总显效率明显高于对照组,差异显著(P0.05)。结论:奥氮平与氯氮平均可以改善急性期精神病症状,但奥氮平具有见效快、疗效好等特点,是治疗急性期精神病值得临床推广的药物之一。     

马来酸氟伏沙明片联合氨磺必利治疗精神分裂症患者的疗效及安全性分析

目的:分析马来酸氟伏沙明片联合氨磺必利治疗精神分裂症患者的临床疗效及安全性。方法:选择我院2014年2月~2018年2月收治的182例精神分裂症患者,按随机数字表法分为对照组99例和研究组83例。对照组采用氨磺必利治疗,研究组在对照组基础上联合马来酸氟伏沙明片治疗。比较两组临床疗效,治疗前后血脂代谢、总胆汁酸(TBA)水平,阳性与阴性症状量表(PANSS)评分,生活质量,及不良发生情况。结果:治疗后,研究组总有效率为91.57%,显著高于对照组(P<0.05);两组治疗前后空腹血糖(FPG)、糖化血红蛋白(HbA1c)、甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白-C(LDL-C)、高密度脂蛋白-C(HLD-C)、总胆汁酸(TBA)水平比较均无统计学意义(P>0.05);两组治疗后PANSS评分均较治疗前显著下降,生活质量评分较治疗前均明显上升,且研究组PANSS评分显著低于对照组,而生活质量评分明显高于对照组,差异均有统计学意义(P<0.05)。治疗过程中,两组均有体重增加、口渴及便秘发生,两组不良反应发生情况比较差异无统计学意义(P>0.05)。结论:马来酸氟伏沙明片联合氨磺必利治疗能够提高精神分裂症患者疗效,对机体糖脂代谢及肝功能影响较小,有良好的用药安全性。     

Inhibition of β-Amyloid Formation by Haloperidol: A Possible Mechanism for Reduced Frequency of Alzheimer's Disease Pathology in Schizophrenia

Abstract: Several reports have suggested that the frequency of Alzheimer's disease (AD) neuropathology is significantly reduced in elderly individuals with schizophrenia (SZ), and it has been proposed that medications used for treatment of SZ may be responsible. A central event in AD pathology is the formation of β-amyloid (Aβ) peptide, which is derived by enzymatic processing of its precursor protein. Haloperidol, an antipsychotic medication commonly used in the treatment of SZ, can act as an inhibitor of select proteinases; hence, we examined the ability of this compound to inhibit Aβ formation by cultured cells. Haloperidol and, to a lesser extent, droperidol inhibited Aβ in a dose-dependent manner. These results may explain the apparent reduction of AD neuropathological changes in elderly patients with SZ as well as provide a possible mechanism for this difference.     

Effects of Chronic Haloperidol and/or Clozapine on Oxidative Stress Parameters in Rat Brain

Decreased antioxidant activity is considered as one of the causes of tardive dyskinesia in schizophrenic patients in a prolonged neuroleptic treatment course. Haloperidol (HAL) has been hypothesized to increase oxidative stress, while clozapine (CLO) would produce less oxidative damage. The objective was to determine whether CLO for 28 days could reverse or attenuate HAL-induced oxidative damage in animals previously treated with HAL for 28 days. HAL significantly increased thiobarbituric acid reactive substances levels in the cortex (CX) and striatum and increased protein carbonyls in hippocampus (HP) and CX and this was not attenuated by CLO treatment. In the total radical trapping antioxidant parameter assay there was a decrease in the HP total antioxidant potential induced by HAL and by treatment with HAL + CLO. Our findings demonstrated that the atypical antipsychotic CLO could not revert oxidative damage caused by HAL.     

奥氮平与碳酸锂分别联合丙戊酸钠治疗双相障碍躁狂发作的临床疗效比较

目的：比较奥氮平与碳酸锂分别联合丙戊酸钠治疗双相障碍躁狂发作的临床疗效,探讨提高双相障碍躁狂发作临床疗效的药物治疗方案。方法：选择双相障碍躁狂发作患者90例,随机均分为A组与B组,A组给予奥氮平联合丙戊酸钠治疗,B组给予碳酸锂联合丙戊酸钠治疗,比较两组患者治疗第2周、第4周、第6周躁狂量表（BRMS）评分、副反应量表（TESS）评分和治疗第6周的临床疗效。结果：两组患者在上述方面比较,差异均具有统计学意义（P〈O．05）,A组临床疗效好于B组。结论：药物治疗双相障碍躁狂发作时,应选择奥氮平联合丙戊酸钠治疗方案,可提高临床疗效,减少用药后副反应。     

奥氮平与碳酸锂分别联合丙戊酸钠治疗双相障碍躁狂发作 的临床疗效比较

目的:比较奥氮平与碳酸锂分别联合丙戊酸钠治疗双相障碍躁狂发作的临床疗效,探讨提高双相障碍躁狂发作临床疗效的药物治疗方案。方法:选择双相障碍躁狂发作患者90例,随机均分为A组与B组,A组给予奥氮平联合丙戊酸钠治疗,B组给予碳酸锂联合丙戊酸钠治疗,比较两组患者治疗第2周、第4周、第6周躁狂量表(BRMS)评分、副反应量表(TESS)评分和治疗第6周的临床疗效。结果:两组患者在上述方面比较,差异均具有统计学意义(P<0.05),A组临床疗效好于B组。结论:药物治疗双相障碍躁狂发作时,应选择奥氮平联合丙戊酸钠治疗方案,可提高临床疗效,减少用药后副反应。     

Formation and Metabolism of Dopamine in Nine Areas of the Rat Brain: Modifications by Haloperidol

The rate of removal of 3,4-dihydroxyphenylacetic acid (DOPAC) in nine rat brain areas (striatum, nucleus accumbens, tuberculum olfactorium, hypothalamus, lateral hippocampus, occipital cortex, brain stem, cerebellum, and retina) was calculated from its exponential decline after monoamine oxidase inhibition by pargyline. The experiments were carried out with rats pretreated with either saline or haloperidol. It appeared that the efficiency with which DOPAC was removed from the brain (expressed by the fractional rate constant k) varied considerably throughout the brain. Haloperidol dramatically decreased the k values, and in addition these effects differed widely in the various brain areas. Similarly to DOPAC, haloperidol had a pronounced retarding effect on the efflux of homovanillic acid (HVA) from the brain. These findings strongly suggest that great care should be taken when drug-induced alterations in DOPAC and HVA concentrations are interpreted as changes in dopaminergic activity. The dopamine (DA) concentrations were measured in the same experiments, but it appeared that the pargyline-induced rise in DA was of limited use for the estimation of the synthesis rate of the amine. We calculated the rate of catecholamine synthesis in the nine brain areas from the rise of 3,4-dihydroxyphenylalanine (DOPA) during decarboxylase inhibition. In saline- as well as in haloperidol-pretreated rats it was found that the total catecholamine synthesis rate in the typical dopaminergic areas (striatum, nucleus accumbens, and tuberculum olfactorium) was of the same order of magnitude as the DOPAC rate of removal. This confirms that DOPAC formation is quantitatively the main route of degradation in these brain areas.(ABSTRACT TRUNCATED AT 250 WORDS)     

High-performance liquid chromatographic method with diode array detection to identify and quantify atypical antipsychotics and haloperidol in plasma after overdose

For toxicological purposes, an HPLC assay was developed for the simultaneous determination of haloperidol and atypical antipsychotics (risperidone, 9-hydroxyrisperidone, olanzapine, clozapine) in human plasma. After a double-step liquid-liquid extraction, compounds were separated on a C(8) column eluted with a gradient of acetonitrile and phosphate buffer 50 mM pH 3.8. A sequential ultraviolet detection was used (260, 280 and 240 nm). Calibration curves were linear in the range 10-1000 ng/ml. The limits of quantification were 5 ng/ml for all drugs. Average accuracy at four concentrations ranged from 93 to 109%. Both inter- and intra-day variation coefficients were lower than 11% for all drugs. This simple and rapid method (run time<15 min) is currently used for poison management.     

Brain neurotransmitter receptor-binding characteristics in rats after oral administration of haloperidol, risperidone and olanzapine

The present study was conducted to characterize the binding of neurotransmitter receptors (dopamine D(2), serotonin 5-HT(2), histamine H(1), adrenaline alpha(1) and muscarine M(l) receptors) in the rat's brain after the oral administration of haloperidol, risperidone, and olanzapine. Haloperidol at 1 and 3 mg/kg displayed significant activity to bind the D(2) receptor (increase in the Kd value for [(3)H]raclopride binding) in the corpus striatum with little change in the activity toward the 5-HT(2) receptor (binding parameters for [(3)H]ketanserin). In contrast, risperidone (0.1-3 mg/kg) showed roughly 30 times more affinity for the 5-HT(2) receptor than D(2) receptor. Also, olanzapine (1-10 mg/kg) was most active toward the H(1) receptor in the cerebral cortex, corpus striatum, and hippocampus, was less active in binding 5-HT(2) and D(2) receptors, and showed the least affinity for alpha(1) and M(1) receptors. In conclusion, haloperidol and risperidone administered orally selectively bind D(2) and 5-HT(2) receptors, respectively, in the rat brain, while olanzapine binds H(1), 5-HT(2), and D(2) receptors more than alpha(1) and M(1) receptors.     

Effects of Subchronic Clozapine and Haloperidol on Striatal Glutamatergic Synapses

Abstract: Subchronic treatment with haloperidol increases the number of asymmetric glutamate synapses associated with a perforated postsynaptic density in the striatum. To characterize these synaptic changes further, the effects of subchronic (28 days) administration of an atypical antipsychotic, clozapine (30 mg/kg, s.c.), or a typical antipsychotic, haloperidol (0.5 mg/kg, s.c.), on the binding of [³H]MK-801 to the NMDA receptor-linked ion channel complex and on the in situ hybridization of riboprobes for NMDAR2A and 2B subunits and splice variants of the NMDAR1 subunit were examined in striatal preparations from rats. The density of striatal glutamate immunogold labeling associated with nerve terminals of all asymmetric synapses and the immunoreactivity of those asymmetric synapses associated with a perforated postsynaptic density were also examined by electron microscopy. Subchronic neuroleptic administration had no effect on [³H]MK-801 binding to striatal membrane preparations. Both drugs increased glutamate immunogold labeling in nerve terminals of all asymmetric synapses, but only haloperidol increased the density of glutamate immunoreactivity within nerve terminals of asymmetric synapses containing a perforated postsynaptic density. Whereas subchronic administration of clozapine, but not haloperidol, resulted in a significant increase in the hybridization of a riboprobe that labels all splice variants of the NMDAR1 subunit, both drugs significantly decreased the abundance of NMDAR1 subunit mRNA containing a 63-base insert. Neither drug altered mRNA for the 2A subunit, but clozapine significantly increased hybridization of a probe for the 2B subunit. The data suggest that some neuroleptic effects may be mediated by glutamatergic systems and that typical and atypical antipsychotics can have varying effects on the density of glutamate in presynaptic terminals and on the expression of specific NMDA receptor splice variant mRNAs. Alternatively, NMDAR1 subunit splice variants may differentially respond to interactions with glutamate.