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.     

Risperidone,quetiapine and chlorpromazine may have induced priapism in an adolescent

Priapism is the prolonged, painful erection of penile tissue not accompanied by sexual arousal. Priapism has been established as a rare adverse drug reaction to drugs such as antipsychotics, psychostimulants, antidepressants, and mood stabilizers. Immediate intervention is needed to prevent destructive and irreversible complications, such as erectile dysfunction, disfigurement, inability of the penis to stay erect, and related social/emotional problems. Antipsychotic‐induced priapism may result from the alpha receptor occupancy property of those drugs. We report the case of a 13‐year‐old suffering from attention deficit–hyperactivity disorder plus conduct disorder with priapism related to antipsychotics. Episodes occurred with risperidone plus methylphenidate, quetiapine plus methylphenidate, and chlorpromazine alone.     

Allergic and photoallergic contact dermatitis to chlorpromazine

Chlorpromazine is known to produce both systemic phototoxic and photoallergic reactions. However, it may also cause photoallergic contact dermatitis and, albeit exceptionally, allergic contact dermatitis (ACD). We present a series of photoallergic contact dermatitis and ACD to chlorpromazine diagnosed at a tertiary centre cutaneous allergy unit between 1980 and 2019.     

利培酮与氯丙嗪对代谢影响随访研究

目的：研究氯丙嗪与利培酮对精神分裂症患者血糖、血脂和体质量的影响。方法：198例精神分裂症患者随机分为氯丙嗪组与利培酮组,随访1年,采集患者空腹血糖、总胆固醇、和体质量的数据。结果：氯丙嗪组和利培酮组总胆固醇、三酰甘油、空腹血糖、糖化血红蛋白、体质量、体质量指数在治疗后均显著升高;以氯丙嗪组更显著为高。结论：氯丙嗪与利培酮对血糖、血脂和体质量的影响不同,但都可使之升高。     

氯丙嗪单独及与顺铂联合应用对人宫颈癌Hela细胞生长的影响

目的:探讨氯丙嗪(CPZ)和顺铂(DDP)联合应用对人宫颈癌Hela细胞株的体外抑制作用。方法:将氯丙嗪、顺铂单独或联合处理Hela细胞,用MTT法检测细胞增殖的抑制率,流式细胞仪检测细胞周期及凋亡,并于用药后不同时间点观察细胞形态学变化。结果:不同浓度的氯丙嗪对细胞生长均有抑制作用,随药物浓度的增加,抑制作用加强。氯丙嗪和顺铂联合应用后抗增殖作用较单一用药显著增强(P<0.05)。二者均可诱导细胞凋亡,联用凋亡率明显增加,并出现G0/G1期细胞阻滞。结论:氯丙嗪可抑制人宫颈癌Hela细胞的增殖,且对顺铂有协同作用。     

Electrical stimulation of the brain stem in freely moving rats: II. Effects on hippocampal and neocortical electrical activity, and relations to behavior

Hippocampal and neocortical slow-wave activity and behavior were recorded in freely moving rats during electrical stimulation (100 pulses/s) of sites throughout the brain stem. Stimulation at many sites (including nucleus cuneiformis; subnucleus compactus; nucleus reticularis oralis, caudalis, and medial gigantocellularis; the pontine central gray; adjacent to the midbrain central gray; centralis superior of the raphe; locus ceruleus) produced hippocampal rhythmical slow activity (RSA; theta) and neocortical low-voltage fast activity (LVFA) during behavioral immobility, especially after treatment with chlorpromazine. At slightly higher currents stimulation at most sites elicited behaviors such as walking, circling, or running, and concomitant RSA and LVFA. Atropine sulfate abolished the RSA and LVFA elicited during immobility by stimulation at most sites. The RSA and LVFA which accompanied centrally elicited locomotion was not abolished by atropine. However, exceptions to the rule that RSA and LVFA occurring during immobility are selectively abolished by atropine were provided by sites in the region of the subnucleus compactus and the nucleus of the posterior commissure. Stimulation in or near the subnucleus compactus produced primarily atropine-resistant RSA whereas stimulation in or near the nucleus of the posterior commissure produced primarily atropine-resistant LVFA. These effects could be obtained while the rats stood totally immobile. In general, the results support the idea that a diffuse ascending system from the brain stem is capable of producing two pharmacologically distinct forms of RSA and LVFA. This neurochemical specificity may be established above the brain stem. The RSA and LVFA which appear during immobility are probably dependent on cholinergic synapses. The neurotransmitter(s) required for the production of atropineresistant (movement-related) RSA and/or LVFA is unknown. It is suggested that the monoamines (noradrenaline, dopamine, and serotonin) are not critically important for the appearance of RSA or LVFA.