• 생물정신의학
• /
• 제6권2호
• /
• pp.246-252
• /
• 1999

Objectives : Daytime drowsiness or sedation and changes in night sleep are commonly seen in patients treated with clozapine. There is, however, very limited information on their degree and nature during the course of treatment. The purpose of this study was to understand the sleep patterns in chronic schizophrenic patients with clozapine treatment over a period of 24 weeks. Method : The sleep pattern was evaluated using a set of 5-point scale questionnaire, to record subjective impressions of the night sleep induction, maintenance and quality, and daytime drowsiness and fatigue. In addition, unusual experiences associated with night sleep were recorded. The sleep questionnaire was repeatedly administered at baseline and at 1, 2, 4, 8, 12 and 24 weeks of drug treatment. At present, data on 12 patients has been collected. Results : All the components of night sleep were significantly improved in the 1st through the 12th week after treatment with clozapine. Daytime drowsiness was significantly higher in the 1st to the 2nd week after the treatment and fatigue was also significantly higher in the 1st to the 4th week after the treatment. Eight patients experienced noticeable increases in salivation during night sleep, and of these, one also reported frequent nocturnal urination and even enuresis. However, all these adverse factors did not affect the major sleep patterns. Conclusions : These findings suggest that the beneficial effects of clozapine on night sleep might last much longer than the undesirable effect of daytime drowsiness and fatigue. In other words, tolerance of the hypnotic action of clozapine might develop late and tolerance of the daytime drowsiness and fatigue might be evident earlier.

• Clinical Psychopharmacology and Neuroscience
• /
• 제16권4호
• /
• pp.505-507
• /
• 2018

Clozapine may be associated with cardiovascular adverse effects including QTc prolongation and, more rarely, with myocarditis and pericarditis. Although rare, these latter cardiovascular adverse effects may be life-threatening and must be immediately recognized and treated. Several cases of clozapine related-pericarditis have been described and often it has a subtle and insidious onset with symptoms that may be often misdiagnosed with psychiatric manifestations (e.g. anxiety, panic or somatization) leading to a delayed correct diagnosis with potential fatal consequences. In the present report we describe the case of a 27-year-old girl with schizoaffective disorder taking long acting aripiprazole and valproate who developed a sudden onset clozapine-related pericarditis during titration phase that resolved with immediate clozapine discontinuation and indomethacin administration. We underline the importance of an early diagnosis of clozapine-related pericarditis and the need to have monitoring protocols to prevent this potentially fatal adverse effect especially when polypharmacy is administered to patients taking clozapine.

• 생물정신의학
• /
• 제8권1호
• /
• pp.140-146
• /
• 2001

In clinical setting, treatment-refractoriness, medication induced tardive dyskinesia and amenorrhea in chronic schizophrenia are frequently problematic. However, there are few guideline solving these problem available to clinicians. The goal of this study was collecting clinical data on clinical effectiveness and predictors of response of switching to olanzapine. We attempted to switch to olanzapine from risperidone and clozapine in chronic 31(risperidone 17, clozapine 14) schizophrenia and schizoaffective disorder patients suffering from sustained symptoms, weekly blood monitoring, medication induced tardive dyskinesia and amenorrhea. Previous antipsychotics dosage was gradually decreased for 2 or 3weeks, at the same time olanzapine dosage was gradually increased. At baseline, after 1 week, after 2 weeks and after 4 weeks we checked Brief Psychiatric Rating Scale, Clinical Global Impression Scale, Sympson-Angus Rating Scale, Barnes Akathisia Rating Scale and followed up after 12 months. Successful switch after 4 weeks was achieved in 25 patients(clozapine 9(64.2%), risperidone 16(94.1%)). Overall, mean BPRS and CGI scores increased significantly. Successful maintenance after 12 months was achieved in 17 patients(clozapine 5(35.7%), risperidone 12(70.5%)). Overall, mean BPRS and CGI scores increased significantly too. Switching to olanzapine from other atypical antipsychotics is recommendable in chronic schizophrenia with treatment refractoriness and drug induced side effect.

• 정신신체의학
• /
• 제28권1호
• /
• pp.36-41
• /
• 2020

연구목적 클로자핀은 뇌심혈관 질환의 발생가능성을 높이는 것으로 알려져 있으며, 혈소판의 활성화 정도는 뇌심혈관 질환의 발생과 관련이 있을 것으로 생각되어왔다. 저자들은 이전 연구에서 단기간의 클로자핀 투여 후 혈소판 활성도가 증가함을 관찰하였다. 본 연구는 이에 대한 후속 연구로 클로자핀을 1년의 기간 동안 장기간 지속 투여하였을 때, 혈소판 활성도에 어떤 영향을 미치는지를 알아보기 위해 시행하였다. 방 법 조현병 혹은 조현정동장애의 치료를 위해 최소 1년의 기간 동안 지속적으로 클로자핀을 투여 받은 환자들의 의무기록을 후향적으로 검토하였다. 혈소판의 활성도는 평균혈소판요소 값을 이용하여 측정하였다. 결 과 총 24명의 환자를 대상으로 하였고, 연구 대상자 중 남성은 9명(37.5%), 여성은 15명(62.5%) 였다. 윌콕슨부호-순위검정에서 초기 및 1년 경과 시점에서의 평균혈소판요소 값 사이의 유의한 변화는 관찰되지 않았다. 결 론 1년간의 지속적인 클로자핀 투여에도 평균혈소판요소의 유의한 변화가 관찰되지 않았다. 단기간의 클로자핀 투여 시 평균혈소판요소 값에 현저한 저하를 관찰하였던 저자들의 이전의 연구 결과를 함께 고려해 볼 때, 본 연구의 결과는 클로자핀 투여 기간에 따라 혈소판의 활성도가 변화할 가능성을 시사한다.

• Animal cells and systems
• /
• 제4권2호
• /
• pp.173-179
• /
• 2000

Evidence suggested that atypical antipsychotics (APs) such as clozapine show less side effects than those of typical APs such as haloperidol and sulpiride. However, little is known about chronic effects of these drugs on changes in gonadotropin releasing hormone (GnRH) mRNA expression and luteinizing hormone (LH) immunoreactivity. Male rats were divided into water-, haloperidol-, sulpiride-, and clozapine-treated groups, and these drugs were administered orally for 4 weeks. The changes in the expression of GnRH mRNA and the LH immunoreactivity were determined in the hypothalamus and pituitary, respectively, using in situ hybridization and immunohistochemistry. GnRH mRNAs were clearly expressed in the water-treated control vats. This was significantly reduced by the chronic treatments with the typical APs, especially with haloperidol, but not with atypical APs clozapine. Likewise, LH immunoreactivity was clearly stained in the control group. While its immunoreativity was significantly reduced by the chronic APs treatments, clozapine treatment showed only slight attenuation. The results show that the atypical APs clozapine has less side effects in the gonadal function than the typical APs haloperidol and the sulpiride. These results suggest that clozapine is a safer drug than the typical APs, at least in the reproductive system.

• 생물정신의학
• /
• 제3권1호
• /
• pp.115-120
• /
• 1996

To investigate characteristic drug effects on the genetic basis, the authors administered haloperidol- the $D_2$ antagonist- and clozapine -the atypical antipsychotics with few extra- pyramidal side effects- to the rats. Then, we edobtain brain specimen from the striatum, prefrontal cortex, and cortical region and compared the degree of c-fos expression. The results are 1) haloperidol was found to produce a rapid and transient induction of dos mRNA expression in striatum as compared with cortex and prefrontal area. 2) clozapine was found to produce rapid induction of c-fos mRNA in striatum and prefrontal area. From these data, we can concluded that the mechanism of action of haloperidol is different from the mechanism of clozapine in gene expression.

• The Korean Journal of Physiology and Pharmacology
• /
• 제23권6호
• /
• pp.467-474
• /
• 2019

Exposure to lead during pregnancy is a risk factor for the development of psychiatric disorders in the offspring. In this study, we investigated whether exposure to low levels of lead acetate (0.2%) in drinking water during pregnancy and lactation causes behavioral impairment and affects the expression of proteins associated with neurodevelopment. Lead exposure altered several parameters in rat offspring compared with those unexposed in open-field, social interaction, and pre-pulse inhibition tests. These parameters were restored to normal levels after clozapine treatment. Western blot and immunohistochemical analyses of the hippocampus revealed that several neurodevelopmental proteins were downregulated in lead-exposed rats. The expression was normalized after clozapine treatment (5 mg/kg/day, postnatal day 35-56). These findings demonstrate that downregulation of several proteins in lead-exposed rats affected subsequent behavioral changes. Our results suggest that lead exposure in early life may induce psychiatric disorders and treatment with antipsychotics such as clozapine may reduce their incidence.

• 정신신체의학
• /
• 제26권2호
• /
• pp.188-193
• /
• 2018

연구목적 클로자핀은 조현병 치료에 널리 처방되는 항정신병약물로, 대사성 부작용 등으로 인한 심뇌혈관질환의 위험을 증가시키는 것으로 알려져 있다. 하지만, 클로자핀이 심뇌혈관질환의 발생에 중요한 영향을 미치는 또 다른 요소인 혈소판 활성 정도에 어떤 영향을 미치는지에 대해서는 알려진 바가 거의 없다. 본 연구에서는 클로자핀 투여 전후 평균혈소판요소 (mean platelet component, MPC) 값 비교를 통하여 조현병 환자에서 클로자핀이 혈소판 활성에 미치는 영향을 알아보고자 하였다. 방 법 2003년 9월 1일부터 2007년 4월 30일까지의 기간 동안 건양대학교 병원 정신건강의학과에서 클로자핀을 새롭게 투여 받기 시작한 환자들을 대상으로 의무기록을 후향적으로 검토 하였다. 최종 통계 분석에는 14명이 포함되었다. 평균혈소판요소는 Bayer ADVIA $120^{(R)}$ system를 이용하여 측정하였다. 결 과 14명의 연구 대상자 중, 남성은 4명(28.60%), 여성은 10명(71.40%)이었으며, 평균 나이는 $37.50{\pm}11.64$세였다. 유병 기간은 평균 $91.00{\pm}93.96$개월 이었으며 피험자들이 마지막 혈액 검사를 한 시점에 복용하였던 클로자핀 용량의 평균은 $337.50{\pm}109.52mg$이었다. 클로자핀 투여 전과 투여 후의 평균혈소판요소 값은 각각 $26.12{\pm}2.22g/dL$과 $25.14{\pm}2.08g/dL$ 이었다. 윌콕슨 부호-순위 검정에서 클로자핀 투여 후 MPC 값이 유의미하게 감소하였다(V=16, p=0.024). 결 론 본 연구의 결과는 클로자핀 투여가 혈소판을 활성화하며, 이로 인해 혈전색전성 질환 등의 발생에 부정적인 영향을 미칠 수 있음을 시사한다. 또한 클로자핀 투여 시 혈소판 활성에 대한 평가를 포함하여 뇌혈관질환의 위험성에 대한 주의 깊은 모니터링이 필요함을 시사한다.

• Bulletin of the Korean Chemical Society
• /
• 제30권7호
• /
• pp.1445-1451
• /
• 2009

New benzotriazoles (5-8) or dibenzodiazepine derivatives (11-18) were synthesized starting from 3-[(2-amino- 4,5-disubstitutedphenyl)amino]-5,5-disubstitutedcyclohex-2-enones (1-4) through internal coupling of their diazonium salts or internal Mannich reaction in the presence of aromatic aldehydes. Pharmacological evaluation of benzotriazole and dibenzodiazepine derivatives for their clozapine-like properties revealed that dibenzodiazepine 11 bearing 4-bromophenyl group exhibited the same antipsychotic activity as the reference drug clozapine while the activity of benzotriazole 7 was 25% lesser than that of clozapine. Moreover, compounds 7 and 11 did not show significant CNS depressant activity as well as no or slight neurotoxicity on contrast to clozapine when tested in mice using forced swim, rotarod and horizontal screen tests.

• 분석과학
• /
• 제35권1호
• /
• pp.24-31
• /
• 2022

Herein, we present a simple, precise, accurate, and ultra-sensitive spectrofluorimetric method for estimation of clozapine (CLZ) in tablets and human plasma was developed and then validated. A highly fluorescent brown-yellowish fluorophore was formed (λ_ex=469 nm, λ_emi=540 nm) as a nucleophilic substitution reaction occurred between CLZ and 4-chloro-7-nitro-2,1,3-benzoxadiazole (NBD-Cl) in alkaline mcllavine buffer (pH 9.0). Optimum values of experimental parameters were carefully determined and optimized. The calibration curve was rectilinear over the concentration range of 80-900 ng mL^-1 with a linear correlation coefficient (r=0.9984). The LOD and LOQ were determined to be 14 ng mL^-1 and 42 ng mL^-1, respectively. The proposed approach has been used successfully to quantification of Clozapine in its commercial formulations and human plasma.