Neuroleptic malignant syndrome in the intensive therapy unit

A case of the neuroleptic malignant syndrome occurred in a 40-year-old male after administration of chlorpromazine while on an Intensive Therapy Unit. Treatment with dantrolene sodium was successful, and a muscle biopsy was examined in the recovery phase of the illness. The importance of this condition and the difficulties in establishing a diagnosis at an early stage in patients on an Intensive Therapy Unit are discussed, along with implications for treatment.     

Effects of chlorpromazine as a systemic vasodilator during cardiopulmonary bypass in neonates

OBJECTIVES: Vasodilator use during cardiopulmonary bypass is important in pediatric cardiac surgery, but the full range of their effects on hemodynamics remains to be clarified. We studied the effects of chlorpromazine, a potent alpha-blocking agent, in neonates. METHODS: Subjects were 60 neonates undergoing arterial switch operations for complete transposition of the great arteries with an intact ventricular septum. Of these, 37 received 2.1 to 6.5 mg/kg of chlorpromazine during cardiopulmonary bypass (CPZ group) and 23 received no vasodilator (control group). We then compared hemodynamic parameters between groups during and early after surgery. RESULTS: The systemic vascular resistance index and mean arterial pressure during cardiopulmonary bypass were significantly lower in the CPZ group (p < 0.05), but systolic pressure 15 minutes after cessation of cardiopulmonary bypass did not differ between groups. The rise in peripheral temperature during rewarming after hypothermia was significantly higher and the acid-base status 40 minutes after cardiopulmonary bypass less acidotic in the CPZ group. Urine output during cardiopulmonary bypass was higher in the CPZ group. CONCLUSIONS: Chlorpromazine effectively counteracts systemic vasoconstriction induced by cardiopulmonary bypass without serious side effects in neonatal cardiac surgery.     

Localization of calcium ions in mixed synapses of Mauthner neurons during exposure to substances altering the conductivity of gap junctions

The pyroantimonate method was used to study the distribution of calcium ions in the mixed synapses of Mauthner neurons after exposure to substances altering the electrotonic conductivity of these synapses mediated by gap junctions (GJ). Ecdysone, an agent which increases GJ conductivity, produced precipitates of calcium pyroantimonate coating the whole postsynaptic surface of the GJ area, making them strongly asymmetrical. Precipitate granules were also seen to appear in the clefts of desmosome-like contacts (DLC). Chlorpromazine, which decreases GJ conductivity, produced precipitates in GJ clefts and on the pre- and postsynaptic membranes. No precipitate formed in DLC clefts. These results demonstrate that ecdysone acts as an agent selectively increasing GJ conductivity without affecting DLC function. Chlorpromazine had a double action, blocking conduction through both GJ and DLC. Thus, studies of agents altering GJ permeability require consideration of the possibility that they may interact with actin-containing structures also involved in the transport of the electrotonic signal.Translated from Morfologiya, Vol. 125, No. 3, pp. 32–35, May–June, 2004.     

氯丙嗪对耐药细胞系K_(562)/AO_2多药耐药逆转作用的研究

目的 :研究氯丙嗪对耐药细胞系K562 /AO2 多药耐药逆转作用。方法 :应用免疫组化观察K562 /AO2 细胞系的耐药蛋白表达情况 ,用MTT法测定不同浓度的氯丙嗪对K562 /AO2 细胞系耐药逆转作用 ,用流式细胞术测定不同浓度的氯丙嗪与K562 /AO2 细胞作用后细胞内罗丹明的蓄积情况 ,用半定量RT PCR法测定氯丙嗪对K562 /AO2 细胞多药耐药基因 (mdr 1)mRNA表达的影响。结果 :K562 /AO2 细胞不但P gp表达阳性 ,而且肺耐药相关蛋白 (lungresistanceelatedprotein ,LRP)表达也阳性 ;氯丙嗪能增强多柔比星对K562 /AO2 细胞的杀伤作用 (单用ADM组、氯丙嗪 0 75 μg/mL ADM组、氯丙嗪 1 5μg/mL ADM组和氯丙嗪 3 μg/mL ADM组对K562 /AO2 的抑制率分别为 5 2 %、 2 5 9%、3 9 1%和 74 8% ) ;增加K562 /AO2 细胞内罗丹明的蓄积 (对照组、氯丙嗪 0 75 μg/mL组、氯丙嗪1 5 μg/mL组和氯丙嗪 3μg/mL组细胞内的荧光强度的均值分别为 1 87、 10 2 8、 48 75和65 63 ) ;对K562 /AO2 细胞mdr 1mRNA表达无明显影响 (对照组mdr 1和 β actin的面积比为0 41,氯丙嗪组为 0 42 )。结论 :氯丙嗪对K562 /AO2 细胞的耐药有较强的逆转作用 ,并呈剂量依赖关系     

Generalization testing with atypical and typical antipsychotic drugs in rats trained to discriminate 5.0 mg/kg clozapine from vehicle in a two‐choice drug discrimination task

Clozapine (CLZ) drug discrimination is used as a preclinical model to evaluate compounds for putative atypical antipsychotic properties. In rats, a 1.25 mg/kg CLZ training dose appears to have greater pharmacological specificity for atypical antipsychotic drugs than the traditional 5.0 mg/kg CLZ training dose; however, methodological differences among studies have precluded a direct comparison between these training doses. In the present study, rats were trained to discriminate a 5.0 mg/kg CLZ dose from vehicle in a two‐choice drug discrimination task using methods similar to those in a previous study from our laboratory that used a 1.25 mg/kg CLZ training dose. Clozapine produced full substitution (≥80% CLZ‐lever responding) for itself at the training dose (5.0 mg/kg). The atypical antipsychotics olanzapine, quetiapine, and ziprasidone also produced full substitution for 5.0 mg/kg CLZ, whereas the atypical antipsychotics risperidone and sertindole produced partial substitution (≥60% CLZ‐lever responding). The typical antipsychotic, thioridazine, produced full substitution for the 5.0 mg/kg CLZ training dose, but the typical antipsychotics chlorpromazine, fluphenazine, and haloperidol failed to substitute for clozapine. In a subgroup of 1.25 mg/kg CLZ‐trained rats, ziprasidone produced strong partial substitution (73.0 % CLZ‐lever responding) for the 1.25 mg/kg CLZ training dose. Based on these findings, some atypical antipsychotic drugs (i.e., quetiapine and ziprasidone) produce full substitution only for the 5.0 mg/kg CLZ training dose, whereas other atypical antipsychotic drugs (i.e., sertindole and risperidone) produce full substitution only for the 1.25 mg/kg CLZ training dose. Thus, both of these training doses are important for the screening of putative atypical antipsychotic drugs with the clozapine drug discrimination assay. Drug Dev. Res. 64:55–65, 2005. © 2005 Wiley‐Liss, Inc.     

奎硫平治疗精神分裂症患者的疗效及生活质量影响

目的:探讨奎硫平与氯丙嗪对精神分裂症患者的疗效及生活质量的影响。方法:对62例精神分裂症患者,随机使用奎硫平和氯丙嗪治疗,疗程3个月。采用阳性与阴性症状量表(PANSS)评定疗效,采用治疗中出现的症状量表(TESS)评定不良反应,以生活质量综合评定问卷(GQOLI-74)评定生活质量。结果:两组均有显著疗效,奎硫平可显著提高生活质量。两组间无显著差异(P>0.05)。氯丙嗪组不良反应比奎硫平组多。结论:奎硫平和氯丙嗪对精神分裂症疗效相当,奎硫平不良反应较少,对提高患者生活质量的效果明显优于氯丙嗪。     

3种抗精神病药对精神分裂症认知功能的影响

目的:探讨阿立哌唑、利培酮和氯丙嗪对首发精神分裂症患者认知功能的影响。方法:56例首发精神分裂症患者分为阿立哌唑组(n=18)、利培酮组(n=24)和氯丙嗪组(n=14),在治疗前和治疗6周进行阳性与阴性症状量表(PANSS)评分,威斯康星卡片分类测验(WCST)、连线测验(A和B)、韦氏成人智力量表(WAIS)中的数字符号和数字广度(顺、逆)测验等神经心理测验。结果:治疗6周后,3组PANSS评分均明显下降,3组之间差异无显著性。阿立哌唑组和利培酮组各项认知功能指标均有不同程度的改善,而氯丙嗪组只有2项(WCST中持续反应数和数字广度测验)较治疗前显著好转。连线测验B阿立哌唑组显著优于利培酮组,其余各指标两组间差异无显著性。阿立哌唑组除WCST中持续反应数、完成分类数和数字广度测验外,其余各指标均显著优于氯丙嗪组;利培酮组除WCST中持续反应数外,其余各指标均显著优于氯丙嗪组。结论:阿立哌唑和利培酮对首发精神分裂症患者认知功能的改善作用相当,均显著优于氯丙嗪。     

利培酮氯丙嗪对首发精神分裂症患者眼动分析NEF的影响

目的探讨眼动分析中凝视点数和反应性探索分析能否作为首发精神分裂症患者的诊断和治疗效果的客观依据以及这两种指标是否受不同抗精神病药物治疗的影响。方法将符合入组标准的53例精神分裂症患者随机分为氯丙嗪组24例、利培酮组29例进行治疗,疗程6w。随机抽取30例正常健康者为对照组,于患者组治疗前及治疗6w末测评三组眼动分析中凝视点数来分析其认知功能的改善情况。结果氯丙嗪组、利培酮组眼动分析中凝视点数评分均显著低于对照组(P<0.01),治疗6w末凝视点数评分虽有显著升高(P<0.01),但仍均显著低于对照组,差异均有极显著性(P<0.01)。结论凝视点数测评可作为首发精神分裂症患者诊断和判定疗效的客观依据,并且可能受药物的影响。     

粉防己碱和氯丙嗪对人胚肺成纤维细胞胶原和透明质酸合成的影响(英文)

目的：研究粉防己碱(Tet)和氯丙嗪(Chl)对人胚肺成纤维细胞胶原与透明质酸(HA)合成的影响,为应用钙拮抗剂防治器官纤维化提供依据.方法:采用[~3H]脯氨酸掺入和放射免疫法分别测定胶原与HA合成.结果:Tet 5—80 μmol L~(-1)和Chl 10—40 μmol L~(-1)均以浓度依赖方式抑制胶原与HA合成.Tet 5—20μmol L~(-1))对细胞无明显毒性却显著抑制胶原与HA合成(P<0.01).结论:Tet在低浓度(5—20μmol L~(-1))时对细胞无明显毒性作用而显著抑制成纤维细胞胶原与HA合成,可望成为治疗器官纤维化的有效药物.     

奎硫平与氯丙嗪治疗精神分裂症的多中心随机双盲对照试验

目的：评价富马酸奎硫平治疗精神分裂症的疗效和安全性，并与经典抗精神病药氯丙嗪对照。方法：本研究采用多中心、随机平行、双盲双模拟对照试验方法。共入组符合研究方案的病例237例，奎硫平组119例，氯丙嗪组118例。两组药物剂量均为每天300—750mg。结果：两组的主要疗效指标阳性和阴性症状量表(PANSS)、简明精神病量表(BPRS)评分在治疗结束时与基线比较均有显著下降(P＜0．01)；根据PANSS减分率评定临床总有效率，奎硫平组的有效率为61．61％，氯丙嗪组的有效率为64．81％，两组之间无显著性差异；奎硫平组的药物不良反应发生率为44．54％，氯丙嗪组的发生率是76．27％。其中以震颤、肌紧张和静坐不能等明显少于对照组；实验室检查两组均无严重异常。结论：富马酸奎硫平是一种新的安全有效的抗精神病药物。