• Archives of Pharmacal Research
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• 제26권11호
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• pp.951-959
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• 2003

A series of typical (chlorpromazine, haloperidol and thioridazine) and atypical (risperidone, quetiapine, clozapine and olanzapine) antipsychotics were tested for effects on integrated bioenergetic functions of isolated rat liver mitochondria. Polarographic measurement of oxygen consumption in freshly isolated mitochondria showed that electron transfer activity at respiratory complex I is inhibited by chlorpromazine, haloperidol, risperidone, and quetiapine, but not by clozapine, olanzapine, or thioridazine. Chlorpromazine and thioridazine act as modest uncouplers of oxidative phosphorylation. The typical neuroleptics inhibited NADH-coenzyme Q reductase in freeze-thawed mitochondria, which is a direct measure of complex I enzyme activity. The inhibition of NADH-coenzyme Q reductase activity by the atypicals risperidone and quetiapine was 2-4 fold less than that for the typical neuroleptics. Clozapine and olanzapine had only slight effects on NADH-coenzyme Q reductase activity, even at 200 $\mu$ M. The relative potencies of these neuroleptic drugs as inhibitors of mitochondrial bioenergetic function is similar to their relative potencies as risk factors in the reported incidence of extrapyramidal symptoms, including tardive dyskinesia (TD). This suggests that compromised bioenergetic function may be involved in the cellular pathology underlying TD.

• 생물정신의학
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• 제3권1호
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• pp.30-36
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• 1996

Tardive dyskinesia is a syndrome of involuntary hyperkinetic abnormal movements that occurs during or shortly after the cessation of neuroleptic drug treatment. Typically, the movements are choreoatheoid. Other movements such as tics and dystonia may be present. Nonetheless, any dyskinesia seen in a neuroleptic-treated patient is not always neuroleptic-induced tardive dyskinesia. The prevalence of tardive dyskinesia varies widely, which reflects many methodological problems, such as differential diagnosis. symptom fluctuation, masking effect of neuroleptics, validated diagnostic criteria. Of suggested risk factors, only old age has been consistently found to be associated with an increased frequency of tardive dyskinesia. Many hypotheses about the pathophysiolgy of tardive kinesia are proposeed, but time-honored ones are not present. No consistently safe and effective treatments are found. Various treatment modalities signifies the general ineffectiveness of these agents for most patients. In general, reduction or cessation of neuroleptics, if possible, is recommended. Remission or improvemets of tardive dyskinesia after neuroleptics withdrawal usually occurs among most patients within three months.

• 대한약리학회지
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• 제30권3호
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• pp.291-297
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• 1994

이 연구에서는 선조체에서 opioid 신경계와 dopamine 신경계의 상호 관계를 알아보기 위해서 morphine을 5m/kg, 20 mg/kg로 10일간 복강내 투여한 후 chlorpromazine, thioridazine, haloperidol, sulpiride, pimozide를 투여하였다. Opioid ${\mu},\;{\delta},\;{\kappa}$ 수용체의 binding의 변화를 관찰하고자 $[^3H]\;DAGO$, $[^3H]\;DPDPE$, 및 $[^3H]\;DPN$ binding assay를 하였으며, 그 결과 morphine (20 mg/kg) 장기 투여된 실험군에서 $[^3H]\;DAGO$, $[^3H]\;DPDPE$, 및 $[^3H]\;DPN$ 결합이 감소되었다. Morphine 20 mg/kg 장기 투여군에 chlorpromazine, thioridazine 주사시에는 morphine 5mg/kg 투여군에 비하여 $[^3H]\;DAGO$ 결합의 감소와, $[^3H]\;DPDPE$, 및 $[^3H]\;DPN$ 결합의 증가를 나타내었고, haloperidol 주사군은 $[^3H]\;DAGO$, $[^3H]\;DPN$ 결합의 감소, 및 $[^3H]\;DPDPE$ 결합의 증가를 나타내었다. Sulpiride, pimozide 주사군은 morphine 5 m/kg 투여군에 비하여 20m/kg 투여군에서 $[^3H]\;DAGO$, $[^3H]\;DPDPE$, 및 $[^3H]\;DPN$ 결합의 증가를 나타내었다. 이상의 결과로 보아 각 약물간의 opioid 결합에 대한 차이점은 있었으나, morphine 5mg/kg 투여군보다 20m/kg 투여군에서 $[^3H]\;DPDPE$ 및 $[^3H]\;DPN$의 결합이 증가의 경향을 보임으로써, 다량의 morphine을 투여했을 때 ${\mu}\;opioid$ 수용체에 비하여 ${\delta}와 ${\kappa}\;opioid$ 수용체가 더 활성화되는 것을 알 수 있었다.

• 생물정신의학
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• 제7권2호
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• pp.198-205
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• 2000

Objectives : Risperidone and clozapine belong to a new generation of antipsychotics that are reportedly more effective and better tolerated than conventional neuroleptics. However, each of these agents costs far more per unit than conventional neuroleptics. The purpose of our retrospective study was to ascertain the total cost and effectiveness of treatment before and after administration of risperidone and clozapine in "revolving door" schizophrenia patients. Method : Data collected on revolving door schizophrenics for 2 years before clozapine and risperidone treatment and for at least 2 years after clozapine and risperidone treatment. Direct cost of inpatient and outpatient treatment was measured. Effectiveness was scaled as "years of mild disability gained". Result : Both risperidone and cloazpine result in higher costs and additional benefits to patients, for example, increased mild disability, reduced number of relapse, and reduced hospital length-of-stay. An ICER of risperidone was less than Rc and ICER of clozapine was greater than Rc. According to decision-analytic this model, risperidone had favorable cost-effectiveness ratios relative to clozapine. Conclusion : We have assumed that risperidone is more cost-effective than clozapine.

• 생물정신의학
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• 제8권1호
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• pp.147-152
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• 2001

Objective : It has been thought that estrogen has neuroleptic like effect in women schizophrenic patients. This study aimed to investigate neuroleptic side-effects severity in women with schizophrenia and to investigate their putative association with variations in sex steroids over menstrual cycle. Based on the estrogen theory, The author hypothesized that parkinsonian side-effects would be exacerbated when estrogen levels were high. Method : 26 schizophrenic women were assessed using the ESRS(Extrapyramidal Symptom Rating Scale) and estrogen analysis. Tests were conducted twice, in the mid luteal and mid follicular phase. Result : It was hypothesized that high level of estrogen would lead to an exacerbation of parkinsonian side-effects but the results indicated that parkinsonian side effects decreased overall when estrogen levels were high. This effects were more marked for the group taking typical neuroleptics than those taking atypical neuroleptics. Conclusion : The results of this study suggest that estrogen and progesteron may reduce the severity of neuroleptic induced extrapyramidal side effects over menstrual cycle in women with schizophrenia. It was concluded that estrogen has different effects on dopamine dynamics in the mesolimbic and mesostriatal pathways according to estrogen, progesteron, catecol estrogen, prolactine.

• 생물정신의학
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• 제1권1호
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• pp.117-123
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• 1994

정신분열증 환자에서 연성 신경학적 증상이 많이 나타나는 것은 많은 연구에서 확인된 바 있으나 이것이 항정신병 약물 복용 등에 의하여 발생하는 부수적인 현상일 가능성이 배제되지 않고 있다. 본 연구는 항정신병 약물 복용군과 비복용군간의 연성 신경학적 증상 발현의 차이를 알아보고자 시도되었다. 항정신병 약물을 전혀 복용하지 않은 28명과 현재 항정신병 약물로 치료 중에 있는 31명의 정신분열증 환자에서 연성 신경학적 증상을 구조화된 평가척도인 한국어판 신경학적 평가척도로 조사하였고 약물용량과 투여기간 및 부작용과의 관계도 알아보았다. 항정신병 약물 비복용군의 신경학적 평가척도의 총점은 $27.14{\pm}5.66$점으로 복용군의 $19.58{\pm}6.55$점보다 유의하게 높았다 (t=-4.76, P<0.001). 하위 기능영역 중에서도 운동조정(t=-5.52, P<0.001), 복합운동활동 순서화(t=-2.20, P<0.05), 기타 항목(t=-5.14, P<0.001)등의 점수는 비복용군에서 높았다. 감각통합 영역은 약물 복용군과 비복용군 사이에 유의한 차이가 없었다. 약물 용량, 연령, 성별 등을 통제한 후의 조사에서는 총점(F=11.13, P=0.00), 운동조정(F=28.46, P=0.00), 기타 항목(F=10.79, P=0.00)등은 약물 비복용군에서 높았으나 복합운동활동 순서화는 이들 공변량의 영향을 받아 약물 복용군과 비복용군사이에 유의한 차이가 없었다. 약물 복용군에서 현재의 항정신병 약물 복용량은 신경학적 평가척도 점수 중 운동 조정 영역과만 유의한 상관성을 보였으며 약물 복용기간, 부작용 등은 연성 신경학적 증상과 상관성이 없었다. 위와 같은 결과로 항정신병 약물은 정신분열증의 신경학적 증상 발현에 상대적인 영향만을 준다고 할 수 있었으며 연성 신경학적 증상이 정신분열증의 주요한 형질 표지자의 하나가 될 가능성이 있다고 하겠다. 또한 향후 보다 통제된 집단에서의 추적연구가 필요할 것으로 생각되었다.

• 생물정신의학
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• 제19권3호
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• pp.146-151
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• 2012

Clozapine is an atypical antipsychotic agent that is more effective than the typical neuroleptics in the treatment of refractory schizophrenia. Recently, there has been an increased recognition of the association of clozapine with myocarditis and cardiomyopathy. Commonly used diagnostic tests have limited sensitivity in diagnosing this potentially life-threatening complication. Here we report a case of 36-year-old male patient who developed fever, tachycardia, and dyspnea after introduction of clozapine. By clinical evaluation and laboratory test we diagnosed the patient with myocarditis and treated him successfully. To our knowledge this is the first case report of clozapine-induced myocarditis in Korea.

• 생물정신의학
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• 제23권2호
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• pp.41-47
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• 2016

Dementia with Lewy bodies (DLB) is the second most common causes of dementia. It can exhibit a variety of clinical symptoms including cognitive decline, cognitive fluctuation, visual hallucinations, parkinsonism, REM sleep behavior disorder, hypersensitivity to neuroleptics and autonomic dysfunctions. Despite more well-known criteria for DLB, there are often misdiagnosis and inappropriate treatment. It gives a lot of clinical burden to the clinician as well as to patients and families. When reducing the misdiagnosis, the burden of all will be reduced. The special concern and solicitation are needed in order not to miss the diagnosis when the cardinal features of DLB may not be volunteered by patients and the caregivers. To control the symptoms, clinicians must find and reduce drugs that can have the negative effects on DLB symptoms. There is limited evidence about specific interventions but available data suggest cholinesterase inhibitors improve the cognitive and behavioral symptoms and menmantine slightly improves the global impression.

• 정신신체의학
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• 제1권1호
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• pp.25-34
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• 1993

The author reviewed the general principle in the use of psychotropics for patients with renal diseases. who have psychiatric problems. Durgs which are dialyzable and metabolized or eliminated by kidney should not be used for patients with renal failure. However, lithium can be effectively used in a single dose$(300{\sim}600 mg/day)$ after each dialysis. though lithium has the double negative components. It is recommended that serum lithium level should be frequently monitored and the dose of lithium should be gradually increased to minimize its side effect Most of other psychotropics such as benzodiazepine anxiolytics tricyclic or tetracyclic antidepressants, and neuroleptics are metabolized in the liver, and they can be used in renal patients. The dose of these drugs should be reduced in two-thirds of the standard dose. In addition. it is necessary for liaison psychiatrists and other physicians to understand the interactions between psychotropics and drugs often used for treatment of renal diseases in order to prescribe psychotropics safely and effectively in renal patients.

• 생물정신의학
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• 제5권1호
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• pp.138-141
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• 1998

Neuroleptic malignant syndrome (NMS) is an uncommon but potentially fatal idiosyncratic reaction to neuroleptics, characterized by muscular rigidity, fever, autonomic dysfunction, and altered consciousness. The major theories to explain NMS is central dopaminergic blockade, but it is unclear. Risperidone is a new antipsychotic drug, a benzisoxazole derivative that blocks dopamine $D_2$ receptor and serotonin type 2 receptor. The comparatively greater serotonin-blocking activity is believed to give risperidone the specific property of not causing any more extrapyramidal side effects than conventional antipsychotics at the optimal dose of 4-8mg/day. It is postulated that risperidone is unlikely to cause NMS. Here, we report a case of risperidone induced neuroleptic malignant syndrome.