• The Korean Journal of Pharmacology
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• v.5 no.2
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• pp.93-103
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• 1969

Saponin, essential oil, fat oil and alkaloidal fraction were fractionated from the ethanol extract of fanax ginseng. Effect of each fraction of Panax ginseng upon the temperature response induced by reserpine, chlorpromazine and nembutal was investigated in mice, so as to secure some hidden facets of each fraction of Panax ginseng acting upon central nervous system. The authors could arrive at some results, that is: (1) Inhibitory effect of Panax ginseng upon temperature decline induced by nembutal and chlorpromazine and potentiating action upon hyperthermia induced by reserpine reside mainly in saponin fraction and slightly in essential oil fraction. (2) The effect of Ginseng saponin on temperature response in nice seems to be related with the liberation of serotonin and histamine.

• The Korean Journal of Pharmacology
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• v.31 no.1 s.57
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• pp.123-133
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• 1995

A number of tricyclic antidepressants appear to have inhibitory action on calmodulin. Although amitriptyline, imipramine and doxepine have been shown to inhibit calcium uptake, oxidative phosphorylation and ATPase activities, effects of amitriptyline, imipramine and doxepine on functional responses of human neutrophils have not been elucidated. In this study, effects amitriptyline, imipramine and doxepine on superoxide and hydrogen peroxide generation, myeloperoxidase release, leukocriene B4 formation and intracellular calcium level were investigated. Superoxide and hydrogen peroxide production in heat aggregated IgG-activated neutrophils were inhibited by amitriptyline, imipramine and doxepine. EDTA, EGTA, verapamil and bepredil inhibited heat aggregated IgG-induced superoxide production. Chlorpromazine, trifluoperazine, staurosporine and H-7 also inhibited it. PMA-induced superoxide production was inhibited by amitriptyline, imipramine, doxepine, chlorpromazine and H-7. Amitriptyline, imipramine, chlorpromazine and trifluoperazine inhibited the myeloperoxidase release by heat aggregated IgG. Productions of $LTB_4$, and 5-HETE in heat aggregated IgG-activated neutrophils were inhibited by amitriptyline, imipramine and doxepine. In neutrophils, elevation of intracellular calcium induced by heat aggregated IgG was inhibited by amitriptyline, imipramine, doxepine, chlorpromazine and EGTA, while verapamil slightly inhibited increase of intracellular calcium and H-7 did not inhibit it. These results suggest that the inhibitory effect of amitriptyline, imipramine and doxepine on respiratory burst, myeloperoxidase release and LTB4 production in heat aggregated IgG-activated neutrophils appears to be ascribed to the inhibition of calcium mobilization, calmodulin and protein kinase C.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.1
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• pp.109-117
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• 1998

Role of $Ca^{2+}$/calmodulin complex in intracellular $Ca^{2+}$ mobilization in neutrophils has not been clearly elucidated. In this study, effects of chlorpromazine, trifluoperazine and imipramine on the intracellular $Ca^{2+}$ mobilization, including $Ca^{2+}$ influx, in C5a-activated neutrophils were investigated. Complement C5a- stimulated superoxide production and myeloperoxidase release in neutrophils were inhibited by chlorpromazine, trifluoperazine and imipramine, except no effect of imipramine on myeloperoxidase release. A C5a-elicited elevation of [$Ca^{2+}$]i in neutrophils was inhibited by chlopromazine, trifluoperazine, imipramine, staurosporine, genistein, EGTA, and verapamil but not affected by pertussis toxin. The intracellular $Ca^{2+}$ release in C5a-activated neutrophils was not affected by chlorpromazine and imipramine. Chlorpromazine and imipramine inhibited $Mn^{2+}$ influx by C5a-activated neutrophils. Thapsigargin-evoked $Ca^{2+}$ entry was inhibited by chlorpromazine, trifluoperazine, imipramine, genistein, EGTA and verapamil, while the effect of staurosporine was not detected. The results suggest that $Ca^{2+}$/calmodulin complex is involved in the activation process of neutrophils. The depressive action of calmodulin inhibitors on the elevation of cytosolic $Ca^{2+}$ level in C5a-activated neutrophils appears to be accomplished by inhibition of $Ca^{2+}$ influx from the extracellular medium.

• The Korean Journal of Pharmacology
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• v.11 no.1 s.17
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• pp.55-60
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• 1975

An animal which is placed in a new environment displays a complex behavioral pattern consisting of locomotion, grooming and rearing. This behavioral pattern is influenced by endogenous and exogenous stimuli, such as hormonal secretion, level of neurohumoral transmitters, drugs and light. It is widely known that the most tranquilizers depressed spontaneous motor activity although their mechanisms of action were different, while antidepressants stimulated except imipramine which showed various action. Until the present time, the hole-board apparatus, which gives rather subjective data, has been used extensively to study the effects of drugs on general activity and exploratory behavior in mice. Recently a new apparatus for mobility measurements, called a 'Selective Activity Meter' has been introduced. This instrument supposedly produces more objective data on activity and behavior. The purpose of the present experiment was to study the influence of psychotropics on motor activity using the Selective Activity Meter. In the experiment, various psychotropic agents such as major tranquilizers(chlorpromazine, haloperidol); minor tranquilizers(meprobamate, diazepam); and antidepressants(amphetamine, imipramine) were used. In each experiment, the drug was administered to five mice and their activity was recorded. Each experiment was run five or more times and the results are based on the mean of each trial. The results are summarized as follows: 1. The group of mice treated with chlorpromazine showed markedly inhibited motor activity in comparison with controls and the inhibitory action of chlorpromazine was shown to be more intense than any of the other drugs used in the test. Haloperidol administration yielded similar results until 60 minutes, but mice showed less inhibition of motor activity than with chlorpromazine after 90 minutes. 2. In the group treated with diazepam, there was strong inhibition of motor activity until 30 minutes, but after 60 minutes the mice showed less inhibition than with chlorpromazine. In the meprobamate group, motor activity was inhibited in a manner similar to that of other tranquilizers, but the inhibition was less than that of diazepam. 3. In the group treated with imipramine, the inhibition developed gradually after ten minutes. 4. The effects of amphetamine did not appear until 30 minutes after administration, but then there was a significant increase in the motor activity.

• 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.

• The Korean Journal of Pharmacology
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• v.12 no.1
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• pp.15-22
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• 1976

The clinical abuse of C.N.S. stimulants during recent years has directed particular attention. Effect of various organs other than C.N.S. was also extensively investigated with those agents. It has been shown that, although there is a wide variation in sensitivity between species, caffeine stimulates gastric secretion in man, cat, guinea pig and dog. Roth and Ivy(1944) reported that caffeine and histamine acted synergistically in stimulating gastric secretion in the cat. Vaille et al(1966) studied that production of pancreatic juice in the rat was enhanced, but bile secretion was not affected by caffeine. In clinical study the effect of chlorpromazine on the external pancreatic secretion in the 24 subjects, the volume fell more than 20% in 7 subjects. (Skajaa et al 1960) It is widely known that C.N.S. stimulants enhanced spontaneous motor activity in the mice, while tranquilizers depressed the activity. Woo (1975) reported that the group of mice treated with chlorpromazine showed markedly inhibited motor activity and in the group of mice treated with amphetamine, there was a significant increase in the motor activity. The purpose of the present experiment was to study the effects of C.N.S. stimulants and depressant on the exocrine pancreas, and on the spontaneous motor activity in the rats. The results obtained are summarized as follows. 1. In animals treated with xanthine derivatives, the volume of pancreatobiliary secretion was markedly increased. 2. Total bilirubin output was elevated markedly in the xanthine derivatives and imipramine treated animals. The bilirubin concentration was increased in xanthine derivatives treated group. 3. The concentration of cholate in the bile was decreased in the chlorpromazine treated group. 4. The activity of lipase in the pancreatobiliary juice was elevated markedly in the xanthine derivatives treated group only. 5. In the all experimental groups, the activity of amylase in pancreatobiliary juice was significantly elevated. 6. In the caffeine treated group, spontaneous motor activity was markedly increased in $30{\sim}60$ minutes, and the amphetamine treated group showed the increased motor activity in first 30 minutes. 7. The group of rats treated with chlorpromazine showed markedly inhibited motor activity after 30 minutes, and the imipramine treated group showed similar result but less inhibition.

• BMB Reports
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• v.37 no.5
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• pp.603-611
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• 2004

Fluorescence probes located in different membrane regions were used to evaluate the effects of chlorpromazine HCl on structural parameters (transbilayer lateral mobility, annular lipid fluidity, protein distribution, and lipid bilayer thickness) of synaptosomal plasma membrane vesicles (SPMVs) isolated from bovine cerebral cortex. The experimental procedure was based on the selective quenching of 1,3-di(1-pyrenyl)propane (Py-3-Py) by trinitrophenyl groups, radiationless energy transfer from the tryptophan of membrane proteins to Py-3-Py, and energy transfer from Py-3-Py monomers to 1-anilinonaphthalene-8-sulfonic acid (ANS). In this study, chlorpromazine HCl decreased the lateral mobility of Py-3-Py in a concentration dependent-manner, showed a greater ordering effect on the inner monolayer than on the outer monolayer, decreased annular lipid fluidity in a dose dependent-manner, and contracted the membrane lipid bilayer. Furthermore, the drug was found to have a clustering effect on membrane proteins.

• The Korean Journal of Pharmacology
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• v.11 no.2
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• pp.19-27
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• 1975

Haloperidol, a butyrophenone, was synthetized by Janssen and introduced for the treatment of psychosis. Although structurally different from the phenothiazines, the butyrophenones share many of their pharmacological properties, such as inhibition of conditioned avoidance response, blocking effect of amphetamine reaction, producing catalepsy, antishock effect and protection against the lethal effects of catecholalmines. Chlorpromazine can lower the arterial blood pressure through its adrenergic blocking activity, its direct effect in relaxing vascular smooth muscle, its direct effect in depressing the myocardium and its action in a complex manner on the central nervous system. In the case of haloperidol, however, was not clarified the mechanism of lowering the blood pressure. The present paper describes the effects of haloperidol on cardiovascular system to investigate the mechanisms of its actions on the arterial blood pressure. The results are followings; 1. In anesthetized cats, intravenous administration of haloperidol and chlorpromazine in the dose of 0.1mg/kg produced a slight decrease in the blood pressure, which followed by complete recovery within $30{\sim}60$ minutes. In the dose of 3mg/kg, however, both produced an abrupt and marked decrease of the blood pressure, which followed by delayed recovery. 2. Haloperidol in the dose ranges of 0.1mg to 3.0mg/kg tended to produce the heart rate slowing in the cats, while chlorpromazine has no effect on the rate. 3. Following administration of haloperidol or chlorpromazine, epinephrine reversal in the arterial blood pressure was observed in the cat, however the responses of norepinephrine and acetylcholine were little affected. 4. In the isolated rabbit atrium the contractility was depressed by haloperidol in the doses over 0.5mg per 100ml, but the rate was not affected. In contrast, the epinephrine-induced contractility was not depressed after haloperidol treatment. However, the increased rate of atrium by epinephrine was partially blocked after haloperidol. 5. In the isolated rabbit aortic strip, epinephrine-induced contraction was blocked by haloperidol. With the above results, it may be concluded that the hypotensive effect of haloperidol was largely due to ${\alpha}$-adrenergic blocking properties and the direct effect in depressing the myocardium as well as its action on central nervous system.

• 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.

• 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.