• Archives of Pharmacal Research
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• v.26 no.11
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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.

• Korean Journal of Biological Psychiatry
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• v.3 no.1
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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.

• The Korean Journal of Pharmacology
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• v.30 no.3
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• pp.291-297
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• 1994

Our purpose was to gain insight into a possible modulatory role for ${\mu},\;{\delta},\;and\;{\kappa}$ opioid receptors by neuroleptics (chlorpromazine, thioridazine, haloperidol, sulpiride, and pimozide) in chronic morphine 5 mg/kg and 20 mg/kg treated mouse striatum. We attempted quantitative receptor assays using highly specific radioligands, $[^3H]\;DAGO\;([D-Ala^2,\;N-Mephe^4,\;Glycol^5]\;enkephalin)$, $[^3H]DPDPE\;([D-Pen^2,\;D-Pen^5]\;enkephalin)$ and $[^3H]\;DPN(diprenorphine)$ to measure the binding affinity in the experimental groups. The decrease of $[^3H]DAGO$ binding was potentiated by sulpiride and pimozide in the chronic morphine treatment (5 mg/kg and 20 mg/kg). The decrease of $[^3H]DPDPE$ binding was inhibited by chlorpromazine, thioridazine, haloperidol, sulpiride, and pimozide in chronic morphine treatment (5 mg/kg and 20 mg/kg). The decrease of $[^3H]\;DPN$ binding was significantly inhibited by chlorpromazine, thioridazine, sulpiride, and pimozide in chronic morphine 20 mg/kg treatment. $[^3H]\;DPN$ binding on the neuroleptics was antagonized by naloxone pretreatment in chronic morphine 20 mg/kg treatment. These findings suggest that neuroleptics influence opposing tonically active on the ${\delta},\;and\;{\kappa}$ opioid receptor compared with ${\mu}$ opioid receptor in the chronic morphine treated mouse striatum.

• Korean Journal of Biological Psychiatry
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• v.7 no.2
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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.

• Korean Journal of Biological Psychiatry
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• v.8 no.1
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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.

• Korean Journal of Biological Psychiatry
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• v.1 no.1
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• pp.117-123
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• 1994

This study was performed to examine the role of neuroleptics may in the development of neurologic soft signs in patients with schizophrenia. Neurologic soft signs were evaluated in 28 neuroleptic naive patients with schizophrenia or schizophreniform disorder and 31 neuroleptic non-naive patients with schizophrenia using a structured tool for measuring neurologic abnormalities, Neurological Evaluation Scale-Korean version(NES-K). Relationship to dose, duration and neurological side effects of neuroleptic treatment were also evaluated. Total scores of NES-K in neuroleptic naive group were significantly higher than those of non-naive group. Scores of motor coordination, sequencing of complex motor acts and others items in functional subcategories were also significantly higher in drug-naive patients. The sensory integration item was not different between two groups. After controlling covariates such ac dose of neuroleptics, age and sex, total scores, motor coordination and others items of NES-K were significantly higher in neuroleptic naive group. However there was no difference between drug naive and non-naive group in the sequencing of complex motor acts item due to effects of these covariates. In neuroleptic non-naive group the dosage of neuroleptics correlated with the motor coordination item, nor were there relationships between duration and side effects of neuroleptic treatment and neurologic soft signs. These findings suggest that neuroleptic treatment may play a only relative role in the development of neurologic soft signs in patients with schizophrenia and these abnormalities may be one of possible trait markers of schizophrenia. To elucidate this opinion, well-controlled, prospective study in same subjects will be helpful.

• Korean Journal of Biological Psychiatry
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• v.19 no.3
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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.

• Korean Journal of Biological Psychiatry
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• v.23 no.2
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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.

• Korean Journal of Psychosomatic Medicine
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• v.1 no.1
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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.

• Korean Journal of Biological Psychiatry
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• v.5 no.1
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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.