• The Korean Journal of Pharmacology
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• v.4 no.1 s.5
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• pp.9-16
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• 1968

The author studied the hemolytic action of phenothiazine derivatives such as promazine, prochlorper azine, perphenazine and thiethylperazine on rabbit erythrocytes, and obtained the following results: 1. Promazine, prochlorperazine, perphenazine and thiethylperazine caused hemolysis in vitro in the following order: Thiethylperazine>perphenazine>prochlorperazine>promazine. 2. Cholesterol inhibited the hemolytic action of prochlorperazine, perphenazine and thiethylperazine, but had no effect on promazine hemolysis. 3. Dextrose, albumin and blood plasma protected erythrocytes against promazine, prochlorperazine, perphenazine and thiethylperazine. 4. The intravenous injection of promazine, prochlorperazine, perphenazine and thiethylperazine caused hemolysis in the same order as they did in vitro.

• Animal cells and systems
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• v.16 no.1
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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.

• 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.

• Journal of Food Hygiene and Safety
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• v.13 no.3
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• pp.232-237
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• 1998

The purpose of this study is to examine the phototoxicity of four phenothiazine derivatives such as chlorpromazine, perphenazine, trifluoroperazine and promethazine, and to investigate the effects of ascorbic acid on their phototoxicity by UVB irradiation. Effects of the test compounds on RBCs were monitored with a spectrophotometer by the method of Kahn et al. The extent of photohemolysis by tested phenothiazine derivatives were increased with their concentration and toxic photoproducts were formed by chlorpromazine and promethazine with preirradiated UVB. Photohemolysis postirradiated chlorpromazine and perphenazine and preirradiated promethazine were decreased with the use of ascorbic acid significantly.

• 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.

• Bulletin of the Korean Chemical Society
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• v.34 no.11
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• pp.3199-3205
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• 2013

The inclusion behavior of sulfobutylether-${\beta}$-cyclodextrin (SBE-${\beta}$-CD) with perphenazine (PPH) was first studied by flow injection (FI)-chemiluminescence (CL) analysis with proposed $lg[(I_0-I_s)/I_s]=lgK_{P-CD}+nlg[C_{PPH}]$ model and molecular docking. Results showed that a 1:1 complex of SBE-${\beta}$-CD/PPH could online form, with the formation constant $K_{P-CD}$ of $2.57{\times}10^7Lmol^{-1}$ at 298 K. The thermodynamic parameters showed that the inclusion behavior of SBE-${\beta}$-CD/PPH was a spontaneous process by hydrophobic interaction. The molecular docking results revealed PPH entered into the larger cavity of SBE-${\beta}$-CD with two hydrogen bonds. Based on the linear relationship of the decrement of luminol/SBE-${\beta}$-CD/PPH CL intensity against the logarithm of PPH concentration ranging from 0.03 to 30.0 ng $mL^{-1}$, the present FI-CL analysis using luminol/SBE-${\beta}$-CD/PPH system was successfully applied to PPH determination in biological fluids and tablets with recoveries from 94.5 to 105.6% and RSDs less than 2.6% (n = 5).

• Environmental Analysis Health and Toxicology
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• v.5 no.1_2
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• pp.45-50
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• 1990

In order to investigate the phototoxicity of five phenothiazine derivatives and one thioxanthen derivative were examined by using in vitro method based on growth inhibition of Candida albicans and red blood cell hemolysis. Effects of the test compounds on RBCs were monitored with a spectrophotometer and a drug PI in the Candida albicans was calculated on the basis of the lowest concentration giving a yeast-free zone. All phenothiazines phototoxic in the red blood cell hemolysis method were positive in the yeast test except promethazine. It was also observed that toxic photo-products were formed by perphenazine and chlorpromazine in the red blood cell hemolysis.

• 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.

• Korean Journal of Biological Psychiatry
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• v.1 no.1
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• pp.124-128
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• 1994

We report a case of antipsychotics induced torsade de pointes in a 42-year-old female schizophrenic patient. The patient had taken perphenazine 20 mg/day, chlorpromazine 100 mg/day, and trifluoperazine 15 mg/day irregularly for about 8 years. She experienced syncope and a few difficulties in breathing. On EKG(electrocardiography), QT interval was delayed and polymorphic QRS complexes and ventricular tachycardia were observed. Following a switch of the antipsychotics to haloperidol, known to have fewest effects on the cardiac rhythms among antipsychotics, the arhythymias disappeared. However after discharge, as dose of haloperidol was increased, the symptoms such as chest discomforts and syncopes reappeared. We concluded that the torsade de pointes was developed by antipsychotics. The most common cause of sudden death in patients receiving antipsychotic treatment appears to be ventricular tochycardia. Therefore, clinician should be well aware of the possible side effects of antipsychotics and be cautious in prescribing such drugs to their patients.

• 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.