• Biomolecules & Therapeutics
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• 제1권1호
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• pp.121-124
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• 1993

To elucidate the effect of antipsychotics and antidepressants on phosphoinositide(Pl) second massenger system, we studied the dose-dependent inhibition of the phosphoinositide-specific phospholipase C(PLC) isozymes, ${\beta}_1,\;{\gamma}_1$ and${\delta}_1,$ by fluphenazine and haloperidol as antipsychotics, and amitriptyline, maprotiline and mianserin as antidepressants. All the antipsychotics and antidepressants tested showed inhibition on at least one of the PLC isozymes with $IC_{50}$ at the concentration between 25 and $250 {\mu}M.$ Maprotiline, mianserin and amitriptyline inhibited 80 to 90% of the activities of all three PLC isozymes at the concentration of $250{\mu}M,$ while haloperidol and fluphenazine inhibited PLC ${\beta}_1$ and${\gamma}_1$ But baclofen didn't inhibit any PLC isozyme. These results suggested that PLC isozymes are inhibited by antipsychotics and antidepessants even though the concentration is high, and these drugs may affect PI signal transduction system by direct inhibition of PLC isozymes.

• 생물정신의학
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• 제5권2호
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• pp.263-277
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• 1998

Conventional high-dose antipsychotics tend to result in more side effects, negative symptoms and dysphoria, and at the same time lower the cognitive function which is already impaired in most schizophrenics. Florid psychotic symptoms, negative symptoms and cognitive impairment greatly impede psychosocial performance and eventual reintegration into society. The reduction of symptom and the improvement of cognitive funtions and social skills are therefore central to the psychiatric rehabilitation process. The purpose of this study was to evaluate the dose-reduction effects of antipsychotics on chronic schizophrenics prescribed conventional high-dose antipsychotics more than 1,500mg equivalent of chlorpromazine. Fifty-one chronic schizophrenics who maintained high-dose antipsychotics for more than three months were randomly assigned to two groups : 20 patients comprised the dose-maintaining group and 31 patients made the dose-reduction group. Over a sixteen weekperiod Positive and Negative Syndrome Scale(PANSS), Extrapyramidal Symptom(EPS), Nurses' Observation Scale for Inpatient Evaluation(NOSIE-30), Continuous Performance Test(CPT), Quality of Life(QOL), and haloperidol/reduced haloperidol blood levels were determined at the base line and after 2, 4, 6, 8, 12, 16 weeks to evaluate the dose reduction effects of high-dose antipsychotics. The results were as follows : 1) Dose-reduction is highly effective in reducing positive and negative symptoms, and general psychopathology. Effects were most prominent at 8, 12, 16 weeks. Among the dose reduction group, positive symptoms in positive symptom group and negative symptoms in negative symptom group were more reduced. 2 Extrapyramidal symptoms showed no significant difference between two groups. But the EPS was reduced time after time within two groups. 3) Hit rates of Continuous Performance Test, which indicate attentional capacity, increased significantly after dose reduction. 4) Haloperidol and reduced haloperidol blood levels decreased until the 4th week, after which they were constant. 5) Total scores of Nurses' Observation Scale for Inpatient Evaluation were unchanged between the two groups. But among the indices, social interest and personal neatness were improved in the dose-reduction group and retardation was aggrevated in the dose-maintaining group. 6) Total quality of life scores were unchanged between two groups. But in the dose maintaining group, satisfaction scores of attention, autonomy, and interpersonal relationship decreased progressively. These findings suggest that the dose reduction of antipsychotics for chronic schizophrenics on programs of high-dose antipsychotics were effective. Dose reduction should therefore be implemanted to spread the rehabilitation and improve quality of life for chronic schizophrenics.

• 생물정신의학
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• 제7권2호
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• pp.159-163
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• 2000

Background : Dopamine receptors are strong candidates for involvement in schizophrenia and are target of a wide variety of antipsychotics. Dopamine $D_5$ receptor(DRD5) gene polymorphisms may be associated with various treatment response. The purpose of our study was define to what significance can be held as a predictor of treatment response in this polymorphism. Method : The total number of 116 Korean chronic schizophrenic patients was assessed after 48 weeks treatment. The Positive and Negative Syndrome Scale(PANSS) was rated for the clinical response to various antipsychotics. With the use of polymerase chain reaction amplification, we assessed this dopamine $D_5$ receptor polymorphism in schizophrenic patients who had been treated with antipsychotics, and related genotype with treatment response, to test the hypothesis that DRD5 polymorphism may lead to varying response to antipsychotics. Result : DRD5 polymorphism was not associated with treatment response to a variety of antipsychotics in chronic schizophrenic patients. Conclusion : Genetic variation of $D_5$ receptors do not predict treatment response to antispychotics.

• 생물정신의학
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• 제10권1호
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• pp.3-19
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• 2003

The use of atypical antipsychotics is limited by occurrence of adverse reactions such as weight gain, despite of their benefits. This article provides a comprehensive review and discussion of the most significant findings regarding obesity-related pathways and integrates these with the known mechanism of atypical antipsychotic action. The focus of this article is primarily on the genetics of obesity related pathways that may be disrupted by atypical antipsychotics. This review also discussed weight gain, hyperglycemia or occurrence of diabetes while being treated with atypical antipsychotics from the point of view of pharmacogenetics. Pharmacogenetic research seeks to uncover genetic factors that will help clinicians identify the best treatment strategies for their patients. It will aid clinically in the prediction of response and side effects, such as antipsychotic-induced weight gain, and minimize the current "trial and error" approach to prescribing in the near future. This article also presents the genetics of both central and peripheral pathways putatively involved in antipsychotic-induced weight gain while providing a comprehensive review of the obesity literature. This article also review obesity related candidate molecules which may be disrupted during atypical antipsychotic drug treatment.

• 생물정신의학
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• 제1권1호
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• pp.124-128
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• 1994

항정신병약물 perphenazine 20mg/day, chlorpromazine 100mg/day. trifluoperazine 15mg/day 등을 투여중인 정신분열증 42세 여자 환자에서 심실성 빈맥의 하나인 torsade de pointes이 나타난 사례를 보고한다. 본 환자는 항정신병약물을 복용하여 오던 중 여러차례 실신과 호흡곤란을 경험하였으며, 심전도상에 QT 간격의 연장과 함께 다양한 모양의 QRS 파를 동반한 심실성 빈맥의 소견이 있어 torsade de pointes을 의심할 수 있었다. 심혈관계에 영향이 적은 항정신병약물인 haloperidol로 바꾼 후 부정맥의 소견이 없다가 퇴원 후 haloperidol을 증량하는 과정에 흉부 불편감, 실신의 증상과 함께 QT 간격의 연장이 다시 발생하여 torsade de pointes이 나타난 원인이 항정신병약물 때문이라는 것을 확인할 수 있었다. 항정신병약물을 사용중인 환자에서 발생하는 급사의 원인으로 심실성 빈맥이 가장 흔하게 제기되고 있다. 따라서 항정신병약물을 처방하는 임상의들은 이에 대한 충분한 지식과 주위가 필요할 것으로 생각된다.

• 정신신체의학
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• 제27권2호
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• pp.111-118
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• 2019

연구목적 본 연구에서는 섬망 증상 조절을 위한 항정신병약물 처방에 영향을 주는 임상적 특징을 알아보고자 한다. 방 법 연세대학교 원주세브란스 기독병원에 입원하여 정신건강의학과에 협진 의뢰된 환자 중, 일반신체질환에 의한 섬망으로 진단된 185명을 대상으로 후향적 의무기록을 조사하였다. 항정신병약물을 사용한 군과 사용하지 않은 군으로 구분하여 임상적 특성을 비교 분석하였다. 결 과 항정신병약물 사용군은 129명(66.5%)으로 정신과약물 사용력이 많았다. 특히 벤조디아제핀계 약물 사용력에서 두 군 간에 유의미한 차이를 보였다. 섬망평가척도 대다수에서 항정신병약물 사용군이 높은 점수를 보였다. 결 론 항정신병약물 사용군은 섬망의 외현 증상이 두드러지며 기저에 벤조디아제핀계 약물 복용력이 높았다. 이는 벤조디아제핀이 섬망의 경과와 외현 증상에 영향을 주었을 가능성이 있다. 임상 현장에서 예후에 영향을 줄 수 있는 섬망의 임상적 특징에 대한 이해가 축적되어야 할 것이다.

• Animal cells and systems
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• 제16권1호
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• pp.20-26
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• 2012

Drug-induced parkinsonism has been associated with an increased risk for Parkinson's disease. Antipsychotic drugs have long been known to cause parkinsonian symptoms. However, it remains unclear whether antipsychotics can directly damage the nigrostriatal pathway. In the present study, we investigated the toxicity mechanism of two typical antipsychotics, perphenazine and trifluoperazine, in a human dopaminergic cell line, SH-SY5Y. Perphenazine and trifluoperazine induced mitochondrial damage as evidenced by fragmentation of mitochondria, activation of Bax, cytochrome c release and a decrease in cellular ATP level. In addition, activation of caspase-3 and apoptotic nuclei were observed following the drug treatment. However, pan-caspase inhibitor did not suppress the cell death induced by the antipsychotics, suggesting that the initiated apoptosis was possibly shifted to necrosis upon caspase inhibition. Damaged mitochondria may have induced oxidative stress since the drug-induced cell death was partially suppressed by an antioxidant. Taken together, our results suggest that perphenazine and trifluoperazine can induce apoptotic cell death in a dopaminergic cell line via mitochondrial damage accompanied by oxidative stress.

• 생물정신의학
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• 제10권2호
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• pp.186-196
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• 2003

Objects:The authors devebped a behavioral modification program for oveweight outpatients with schi-zophrenia and bipolar disorder will had teen treated with atypical antipsychotics, and evaluated the applicability of this program to outpatients Methods:Two men and nine women who had been treated with atypical antipsychotics and will had gained at least 5 percent of their pre-treatment body weight for 10 weeks, attended a behavioral modification program. The patients' weight, body mass index and the diet-activity scale were assessed and were compared with those of a matched comparison group will dd not attend the behavioral modification program Results:The body weight of patients who attended the behavioral modification program reduced with statistical significance, The treatment group showed significant improvement in diet-related items but not in activity-related items of the diet-activity scale Conclusions:This study suggested the applicability of a eehavioral mcdification program on weight reduction to overweight patients taking atypical antipsychotics for the frrst time in Korea Additional large scale studies are needed to validate the effectiveness of this program.

• 생물정신의학
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• 제11권1호
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• pp.49-53
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• 2004

Objective:A Comparison of QTc prolongation for various antipsychotics and an analysis of QTc prolongation for the various types of serotonin transporter polymorphism were performed. Method:EKG was checked, followed by QTc measurement as Bazett's correction, and the serotonin transporter polymorphism was examined in 110 chronic schizophrenia patients were performed EKG before 24 weeks ago. We defiened QTc prolongation as over 450ms. The risk factor of sudden cardiac death were defiend as QTc prolongation and or 60ms in delta value. Result:The prevalence of QTc prolongation in this study was 7.3%, and the prevalence of over 60ms was 4.5%. Patients who had the risk factors were 10(9.1%). 6/52 who prescribed atypical antipsychotics and 2/58 who prescribed haloperidol showed QTc prolongation. The prevalence who had the risk factor of sudden cardiac death were 16% in atypical antipsychotics group, 3.4% in haloperidol group. QTc prolongation were observed more frequently in l/l type than s/s type. l allele frequency were 50% in QTc prolongated group, 19% in not prolongated group. l allele had an association with QTc prolongation(p<0.01). Conclusion:The prevalence of QTc prolongatin was frequent in chronic schizophrenia patients who were prescribed atypical antipsychotics. It has strong association with l allele of 5-HTTLPR.

• 한국융합학회논문지
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• 제9권12호
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• pp.207-216
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• 2018

한국은 지적장애인에 대한 항정신약의 사용 실태를 국가적으로 조사한 연구가 없어 항정신약 사용의 문제점이나 개선사항을 파악하기 어렵다. 따라서 본 연구의 목적은 지적장애인에게 처방되는 항정신약의 사용 실태를 국가적으로 조사한 일본의 동향을 분석하여 한국에서의 조사를 위한 기초 자료를 제공하고자 한다. 연구 방법은 일본의 J-STAGE, 메디칼온라인, 코호트 연구에서 정신박약, 정신지체, 지적장애, Psychotropic, Antipsychotic, 행동장애로 검색하여 유효한 논문들을 비교 분석하였다. 연구 결과는 첫째, 지적장애인에게 처방되는 다양한 항정신약물의 치료 효과에 대한 정확한 평가가 곤란하며, 둘째, 부작용을 쉽게 알아내지 못하는 동향이 높으며 셋째, 약물 간의 상호작용에 의한 부작용의 가능성에 대한 문제가 제기되고 있음을 알 수 있었다. 이 결과는 향후 한국의 지적장애인에게 보다 안전한 항정신약의 사용을 보장하기 위한 연구와 조사는 물론 개선 방법을 모색하는데 기초 자료가 될 것이다.