• Psychiatry investigation
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• v.15 no.11
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• pp.1064-1070
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• 2018

Objective Several cell line studies have demonstrated thioridazine's anticancer, multidrug resistance-reversing and apoptosis-inducing properties in various tumors. We conducted this nationwide population-based study to investigate the association between thioridazine use and cancer risk among adult patients with schizophrenia. Methods Based on the Psychiatric Inpatient Medical Claim of the National Health Insurance Research Database of Taiwan, a total of 185,689 insured psychiatric patients during 2000 to 2005 were identified. After excluding patients with prior history of schizophrenia, only 42,273 newly diagnosed patients were included. Among them, 1,631 patients ever receiving thioridazine for more than 30 days within 6 months were selected and paired with 6,256 randomly selected non-thioridazine controls. These patients were traced till 2012/12/31 to see if they have any malignancy. Results The incidence rates of hypertension and cerebrovascular disease were higher among cases than among matched controls. The incidence of hyperlipidemia, coronary artery disease and chronic pulmonary disease did not differ between the two groups. By using Cox proportional hazard model for cancer incidence, the crude hazard ratio was significantly higher in age, hypertension, hyperlipidemia, cerebrovascular disease, coronary artery disease and chronic pulmornary disease. However, after adjusting for other covariates, only age and hypertension remained significant. Thioridazine use in adult patients with schizophrenia had no significant association with cancer. Conclusion Despite our finding that thioridazine use had no prevention in cancer in adult patients with schizophrenia. Based on the biological activity, thioridazine is a potential anticancer drug and further investigation in human with cancer is warranted.

• Journal of Food Hygiene and Safety
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• v.7 no.4
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• pp.143-147
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• 1992

This study was conducted to investigate the effects of ascorbic add on their phototoxicity of four phenothiazine derivatives such as chloropromazine, perphenazine, trifluoperazine and thioridazine. Effects of the test compounds on RBes were monitored with a spectrophotometer by the method of Kahan et al. The extent of photohemolysis by chlorpromazine, perphenazine and thioridazine were decreased with the use of ascorbic acid. It was observed that toxic photoproducts were formed by chlorpromazine and thioridazine with preirtadiated. Although red blood cell hemolysis by preirradiated chlorpromazine was decreased with the use of ascorbic acid but thioridazine was not changed.

• Journal of Food Hygiene and Safety
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• v.9 no.1
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• pp.15-21
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• 1994

The mutagenic activity of four phenothiazine derivatives such as chlorpromazine, perphenazine, trifluoperazine and thioridazine in conjunction with UV-A irradiation or not based on the Ames plate incorporation test in the presence and absence of liver microsomal enzyme(S9 fraction). None of these compounds and their photo-excited were detected as mutagen in the Salmonella microsome assay with TA 98 and TA 100.

• 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.

• 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.

• Environmental Analysis Health and Toxicology
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• v.15 no.1_2
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• pp.13-18
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• 2000

A few in vitro methods were developed to compare the result on the phototoxicity of phenothiazines. By the MTT assay, the Candida test, and the RBC photohemolysis, the phototoxicities of UVA and UVB irradiation were measured. This paper presents the comparisons of methods which are effective to measure the phototoxicities of the chemicals causing phototoxicity and photoallergy. The tested chemicals of phenothiazines include Chlorpromazine, Promethazine, Perphenazine, Chlorprothixene, Trifluoperazine and Thioridazine. Each chemical represented variable results according to the test methods. MTT assay shows the most sensitive method.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.101-101
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• 1993

사용한 CPZ, PPZ, TFZ 및 TRZ의 약물이 UVA조사에 의해 용혈독성이 크게 나타났으며 CPZ, PPZ, TRZ에 의한 광용혈정도는 ascorbic acid에 의해 유의성 있게 감소되었다. 또한 적혈구를 가하기 전 각 약물을 미리 조사시켜 생성된 물질에 의한 광용혈현상의 광독성생성물질은 chlorpromazine과 thioridazine에서 보여졌으며, cholrpromazine의 광독성생성물질에 의한 적혈구 용혈현상만 ascorbic acid에 의해 감소되었다. UVA조사전 후의 각 약물에 대한 TA98, TA100에서의 발암성은 인정되지 않았다.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.328-328
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• 1994

광독성 및 광알러지를 일으키는 제반 약물이나 화학물질의 안정성과생체 이용율을 높이고 현재까지 확실하게 규명되어있지 않은 약물 및 화학물질에의한 광독성 광알러지성의 기전을 이해하고 설명할수있는 학문적 기초를 확립 하고저 phenothiazines 중 몇가지 약물를 택하여 적혈구를 이용한 광용혈 여부와 이에 미치는 ascorbic acid, butyl hydroxy anisole, dibutyl hydroxy toluene의 영향을 조사하였다. 각 약물 농도를 50$\mu\textrm{g}$/m1로 하고 UVA(350nm.2.5 ㎽/cm)조사시간은 30분으로 하여 적혈구의 광용혈현상을 Kahn등의 방법에의해 spectrophotometer로 측정한결과 chlorpromazine, perphenazine, thioridazine매 의한 광용혈정도는 ascorbic acid에의해 유의성 있게 감소되었다. 또한 적혈구를 가하기 전 각 약물을 미리조사시켜 생성된 물질에의한 광용혈현상의 광독성생성물질은 chlor- promazine과 thioridazine에서 보여졌으며, chlorpromazine의 광독성생성물질에 의한 적혈구 용혈현상만 ascorbic acid에의해 감소되었다.

• YAKHAK HOEJI
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• v.33 no.4
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• pp.211-218
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• 1989

Twenty-six injectable drug products, many of which are administered by i.v. infusion, were studied for loss from aqueous solutions stored in polyvinyl chloride (PVC) infusion bags for various periods of time. The PVC infusion bags were stored in the dark room at room temperature for up to one month. Drugs stored in glass bottle served as controls. The solutions were assayed Spectrophotometrically at regular intervals. The effect of drug concentration and pH on the loss of drug from solution were studied. Octanol-water partition coefficients were used as a guage of lipid solubility of drugs. The elution of di(2-ethylhexyl)phthalate(DEHT) from PVC infusion bags was studied. For most of the drug studied, minimal loss from the aqueous solutions were observed over periods of storage time. Six of the drug products - Thiopental sodium, Hydralazine HCl, Thioridazine HCl, Trifluoperazine 2HCl, Metronidazole, Chlorpromazine HCl - were found to be lost a substantial extent. DEHP was found to be migrating from PVC infusion bags.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.9 no.2
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• pp.247-252
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• 1998

Neuroleptic malignant syndrome(NMS) is an acute, potentially fatal, idiosyncratic reaction to neuroleptic medication. Early recognition and intensive care are crucial. An important issue is whether NMS will recur after initial recovery and subsequent use of neuroleptic medication. The authors presented with a male adolescent who had suffered a bipolar disorder manic episode and been taking clozapine after recovering from MNS. He had been admitted into a psychiatric ward once before and similarly diagnosed. On the second admission, he showed muscle rigidity, autonomic instability, mild fever, severe diaphoresis, and altered mental status on the fourth hospital day following a haloperidol injection. He was diagnosed with NMS, according to the clinical signs and laboratory data. After the use of antipsychotics was discontinued, he was moved to intensive care unit and given dantrolene. His condition began to improve about 48 hours after the onset of NMS. Due to manic behavior, he returned to the psychiatric ward. On the 21 st hospital day, clozapine was administered to counter the manic symptoms. The final dose was 350mg and showed good remission signs without further recurrence of NMS.