• 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.

• 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.

• The Korean Journal of Pharmacology
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• v.9 no.1
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• pp.23-37
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• 1973

This paper presents the effect of chronic administration of psychotropic drugs on rats. The experimental animals were litter mates (average initial body weight $47{\pm}1.1g$) whose mother were bred at our laboratory. Each litter mate was treated as one group. Control animals were treated with tap water and each experimental group was treated with caffeine citrate 0.1%, nialamide 0.1%, ethyl alcohol 2.5%, phenobarbital sod. 0.1%, diphenylhydantoin 0.1%, chlorpromazine 0.1%, reserpine 0.005%, diazepam 0.01%, chlorpheniramine 0.01% solutions respectively in drinking water over a period of ten weeks. All rats were allowed food and drinking water ad libitum. The mortality rate and the per cent increase of body weight were recorded weekly throughout the course of the experiment. The effects of above agents on the pentobarbital sleeping time, gastric secretion, and brain and liver weights were studied at the end of ten weeks treatment. The obtained results are summarized as follows: 1. Mortality rate was highest in the groups treated with phenobarbital and chlorpromazine respectively. Through the experimental period (ten weeks), the mortality rate was higher in earlier stage than in the later period. 2. During the period of prolonged administration of psychotropic drugs, only diazepam treated group showed remarkable difference in per cent increase of body weight from the control group of rats. 3. Acute treatment with psychotropic drugs delayed the onset of pentobarbital sleeping time. In contrast, the sleeping time was significantly shortened (p<0.001) when the rats were treated chronically with those agents. 4. The effects of chronic treatment with phenobarbital or diphenylhydantoin on the gastric secretion are as follows: the total acidity was remarkably decreased while the pH was increased. 5. The brain weight was significantly decreased in the ethyl alchol and in the chlorpheniramine treated groups, in the mean time, there was no change in liver weight treated with any psychotropic drugs.

• 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.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.1
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• pp.97-105
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• 1997

The regulatory role of cyclic nucleotides in the expression of neutrophil responses has been examined. fMLP-stimulated superoxide production in neutrophils was inhibited by dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP), histamine, adenosine + theophylline, cAMP elevating agents, and 8-bromoguanosine 3' ,5' -cyclic monophosphate (8-BrcGMP) and sodium nitroprusside, cGMP elevating agents. Staurosporine, a protein kinase C inhibitor, genistein, a protein tyrosine kinase inhibitor and chlorpromazine, a calmodulin inhibitor, inhibited superoxide production by fMLP, but they did not further affect the action of DBcAMP on the stimulatory action of fMLP. DBcAMP, histamine, adenosine+theophylline and genistein inhibited myeloperoxidease release evoked by fMLP, whereas BrcGMP, sodium nitroprusside and staurosporine did not affect it. The elevation of $[Ca^{2+}]_i$ evoked by fMLP was inhibited by genistein and chlorpromazine but was not affected by staurosporine. DBcAMP exerted little effect on the initial peak in $[Ca^{2+}]_i$ response to fMLP but effectively inhibited the sustained rise. On the other hand, BrcGMP significantly inhibited both phases. fMLP-induced $Mn^{2+}$ influx was inhibited by either DBcAMP or BrcGMP. These results suggest that fMLP-stimulated neutrophil responses may be regulated by cAMP more than cGMP. cAMP and cGMP appear not affect stimulated responses by direct protein kinase C activation. Their regulatory action on the stimulated neutrophil responses may be not influenced by other activation processes.

• The Korean Journal of Pharmacology
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• v.23 no.1
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• pp.33-44
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• 1987

NADPH oxidase dependent superoxide generation and phagocytosis in neutrophils stimulated with opsonized zymosan or heat aggregated IgG were coincided with the process of calcium uptake. The responses in activated neutrophils were enhanced with increasing concentrations of extracellular calcium and these effects were significantly inhibited by calcium chelators, EGTA and EDTA. The superoxide generation in activated neutrophils was reduced by dantrolene and chlorpromazine. Calcium antagonists, bepredil, diltiazem, verapamil, nifedipine and nimodipine effectively inhibited the calcium uptake, superoxide generation and phagocytosis in activated neutrophils, and NADPH oxidase activity was also inhibited. The results suggest that calcium antagonists may inhibit the superoxide generation and phagocytosis in activted neurtophils by the inhibition of calcium influx and by the action on intracellular redistribution of calcium and NADPH oxidase system.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.35 no.3
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• pp.193-202
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• 2009

This study was done to assess an alternative method as a replacement of in vivo phototoxicity test. The human fibroblasts were exposed to several phototoxic chemicals (promethazine, chlorpromazine chlortetracycline, 8-methoxypsoralen, neutral red, bithionol) and non-phototoxic materials (cinnamic aldehyde, p-aminobenzoic acid, sodium lauryl sulfate, L-cysteine). The cell viability was measured by neutral red uptake (NRU) assay. The results of the NRU phototoxicity (PT) assay showed a close agreement with in vivo test except bithionol. We also have tested the cosmetic ingredients including $Medimin^{(R)}$ A, $Medimin^{(R)}$ D, $LG^{(R)}$ 106W, $Phytoclear^{(R)}$ EL-1, Carex humilis L. extract, Canna indica L. extract, Salvia miltiorrhira Bunge extract, $Parsol^{(R)}$ MCX and $Parsol^{(R)}$ 1789. Most materials except Salvia miltiorrhira Bunge extract did not show any phototoxicity.

• The Korean Journal of Zoology
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• v.32 no.1
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• pp.34-39
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• 1989

Ouabain, strychnine sulfate, caffeine sodium benzoate and chlorpromazine hydrochloride were introduced intraperitoneally into male mice for 7, 14 and 21 days to induce the changes in the relative percentages of lactate dehydrogenase isozymes. The five isozymes in brain, heart and kidney tissues were electrophoresed on cellulose acetate strip and subjected to densitometry. Ouabain caused a drastic increase of B$_4$isozymes only in brain tissues. The two stimulants altered the relative percentages of $A_4$and B$_4$isozymes conspicuously in brain tissues, whereas virtually no redistributions of five isozymes were occurred by the depressant except B$_4$isozymes in brain and heart tissues. On the basis of these observations, it might be suggested that the changes in intracellular concentration of sodium and calcium ions are not the cause of the isozyme redistributions and that Organization of plasma membrane could be one of the factors involved in the tissue specificity of lactate dehydrogenase isozymes in vertebrates.

• The Korean Journal of Pharmacology
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• v.29 no.1
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• pp.107-120
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• 1993

Particulate or soluble stimuli appear to stimulate phagocytic cell's response by the change of $Ca^{2+}$ mobilization and by the activation of protein kinase C. In contrast, it is reported that activation of protein kinase C could attenuate agonist-stimulated elevation of $Ca^{2+}i$ in neutrophils. PAF elicited an increase of $Ca^{2+}i$ in peritoneal macrophages in a dose dependent fashion and $Ca^{2+}$ extrusion was accompanied. PAF-induced elevation of $Ca^{2+}i$ was not affected by TMB-8, verapamil and TTX. TEA stimulated PAF-induced mobilization of $Ca^{2+}i$ and delayed lowering of $Ca^{2+}i$. Five mM EGTA almost completely inhibited PAF-induced mobilization of $Ca^{2+}i$. After the addition of PAF, membrane permeability was markedly increased up to 5 min and then slowly increased. PAF-induced LDH release was slightly decreased by EGTA plus TMB-8. PAF-stimulated superoxide generation was inhibited by EGTA, TMB-8 and verapamil but not affected by TTX and TEA. PAF-induced elevation of $Ca^{2+}i$, increased membrane permeability and superoxide generation were inhibited by IQSP, chlorpromazine and propranolol. PAF-induced LDH release was significantly inhibited by chlorpromazine and minimally decreased by propranolol. After the pretreatment with PMA, the stimulatory effect of PAF on the elevation of $Ca^{2+}i$ and LDH release in macrophages was significantly decreased. These results suggest that PAF may exert the stimulatory action on peritoneal macrophages of mouse by the elevation of $Ca^{2+}i$ and by the activation of protein kinase C. Preactivation of protein kinase C appears to attenuate the stimulatory action of PAF on macrophage response.