• Toxicological Research
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• v.22 no.2
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• pp.109-116
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• 2006

Safety pharmacology studies are conducted to investigated the potential undesirable pharmacodynamic effects of a substance on physiological functions in relation to exposure in the therapeutic range and above. In the International Conference on Harmonisation (ICH), the guideline 'S7A: Safety Pharmacology Studies for Human Pharmaceuticals' has been developed and reached Step 5 of the ICH process in 2001. Now the Korea Food and Drug Administration (KFDA) are going to transfer 'The Guideline for General Pharmacology' into 'The Guideline for Safety Pharmacology'. Safety pharmacology studies should be performed in compliance with Good Laboratory Practice (GLP). Thus, the present paper reviews the Japanese GLP guidelines for pharmaceuticals to help the conduct and inspection of safety pharmacology studies in compliance with GLP. We also reviewed the ICH guidelines 'S7B revised : The Nonclinical Evaluation of the Potential for Delayed Ventricular Repolarization (QT Interval Prolongation) by Human Pharmaceuticals' and 'E14 : The Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-antiarrhythmic Drugs' to apply our drug approval systems.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.6
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• pp.525-530
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• 2013

Multidrug resistance 3 (MDR3) is expressed on the canalicular membrane of the hepatocytes and plays an important role in protecting the liver from bile acids. Altered ABCB4 gene expression can lead to a rare hepatic disease, low phospholipid-associated cholelithiasis (LPAC). In this study, we characterized 3 ABCB4 mutations in LPAC patients using various in vitro assay systems. We first measured the ability of each mutant to transport paclitaxel and then the mechanisms by which these mutations might change MDR3 transport activity were determined using immunoblotting, cell surface protein biotinylation, and immunofluorescence. Through a membrane vesicular transport assay, we observed that the uptake of paclitaxel was significantly reduced in membrane vesicles expressing 2 ABCB4 mutations, F165I and S320F. Both mutants showed significantly decreased total and cell surface MDR3 expression. These data suggest two missense mutations of ABCB4 may alter function of MDR3 and ultimately can be determined as LPAC-causing mutations.

• Journal of Physiology & Pathology in Korean Medicine
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• v.29 no.6
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• pp.443-450
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• 2015

The purpose of this study was is to understand how the network pharmacology databases of traditional medicine in China are established and provide suggestion for successful implementation in Traditional Korean Medicine. We searched for network-pharmacology-related TCM Databases provided on the internet, and analysed their contents. Then, we compared herbs related to Sasang with herbs of the TCM Databases. We chose 8 network-pharmacology-related TCM Databases. They shared information about compounds, herbs, formulae, drugs, targets and diseases, and provided interaction networks between these components. In comparison with herbs related to Sasang, TCMSP Database did not have information about 99 herbs in total, and 25 herbs included in major Sasang formulae. The implications and recommendations for Traditional Korean Medicine researches were discussed. Based on the results of this primary study, more related studies should be carried out in the future.

• Archives of Pharmacal Research
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• v.20 no.5
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• pp.516-518
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• 1997

In conclusion, biochemical analysis revealed that GTS inhibited the methamphetamine-induced DA increase and the methamphetamine-induced DOPAC decrease in the mouse striatum. These results indicate that GTS could modulate the methamphetamine-induced striatal dopaminergic neuronal systems.

• 대한임상약리학회:학술대회논문집
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• 2001.12a
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• pp.41-41
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• 2001

• The Korean Journal of Pharmacology
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• v.30 no.2
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• pp.227-242
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• 1994

The general pharmacological effects of a new anthracycline anticancer agent, DA-125 $[7-0-(2,\;6-dideoxy-2-fluoro-{\alpha}-L-talopyranosyl)-adriamycinone-14-{\beta}-alaninate{\cdot}HCI]$ were investigated in mice, rats, guinea pigs, rabbits and dogs. Intravenous administration of DA-125 presented no significant effects on the central and peripheral nervous systems of ICR mice except a decrease in the numbers of acetic acid-induced writhing response at a dose of 10 mg/kg. In anesthetized rats and dogs, DA-125 produced a transient depression of blood pressure and an increase in heart rate, but did not affect the peripheral blood flow in the isolated ear vessels of rabbits and the mechanical functions of the isolated hearts of guinea pigs. No significant effects were observed on the gastrointestinal functions and the contractilities of smooth muscle preparations obtained from guinea pig trachea, rabbit ileum, pregnant and non-pregnant uterus and vas deferens of rats. DA-125 Increased the contractility of the isolated ileum of guinea pigs in a dose range of $10^{-6}{\sim}10^{-9}g/ml$, and also increased, but weaker than adriamycin, the vascular permeability in rat skin. DA-125 had no effect on the kallikrein-induced increase in permeability and the permeability of the visceral organs. DA-125 did not adversely affect the liver function and the blood coagulation system, and did not induce hemolysis in vitro. It is concluded from the results that the general pharmachological effects of DA-125 are similar to or weaker than those of adriamycin, and that little adverse effects are anticipated with a therapeutic dose range.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.2
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• pp.147-155
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• 1999

Antioxidant effects of serotonin and L-DOPA on neuronal tissues were examined by studying the oxidative damages of brain synaptosomal components. The study further explored the mechanism by which they exert protective actions. Serotonin and L-DOPA (1 ${\mu}M$ to 1 mM) significantly inhibited lipid peroxidation of brain tissues by either $Fe^{2+}$ and ascorbate or t-butyl hydroperoxide in a dose dependent fashion. Protective effect of serotonin on the peroxidative actions of both systems was greater than that of L-DOPA. Protein oxidation of synaptosomes caused by $Fe^{2+}$ and ascorbate was attenuated by serotonin and L-DOPA. Protein oxidation more sensitively responded to L-DOPA rather than serotonin. Serotonin and L-DOPA (100 ${\mu}M$) decreased effectively the oxidation of synaptosomal sulfhydryl groups caused by $Fe^{2+}$ and ascorbate. The production of hydroxyl radical caused by either $Fe^{3+},$ EDTA, H_2O_2$ and ascorbate or xanthine and xanthine oxidase was significantly decreased by serotonin and L-DOPA (1 mM). Equal concentrations of serotonin and L-DOPA restored synaptosomal $Ca^{2+}$ uptake decreased by $Fe^{2+}$ and ascorbate, which is responsible for SOD and catalase. Protective effects of serotonin and L-DOPA on brain synaptosomes may be attributed to their removing action on reactive oxidants, hydroxyl radicals and probably iron-oxygen complex, without chelating action on iron.

• Journal of Physiology & Pathology in Korean Medicine
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• v.35 no.5
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• pp.125-131
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• 2021

The scientific understanding of Korean medicine theory remains largely unknown, since there is a lack of proper methods to investigate its complex and unique characteristics. Here, we introduce a drug-centered approach, a novel method to investigate Korean medicine theory by analyzing the mechanisms of herbal medicines. This method can be effectively conducted by employing network pharmacology that can analyze the systems-level mechanisms of herbal medicines on a large scale. Firstly, we introduce the method of network pharmacology that are applied to analyze the mechanisms of herbal medicines in a step-by-step manner. Then, we show how the drug-centered approach employing network pharmacology can be applied to investigate Korean medicine theory by describing studies that identify the biological correlates of the cold-hot nature of herbs, spleen qi deficiency syndrome, or Sasang constitution. Finally, we discuss the limitations and future directions of the proposed approach in two aspects: The methods of network pharmacology for a drug-centered approach and the process of inferring Korean medicine theory through it. We believe that a drug-centered approach employing network pharmacology will provide an advanced scientific understanding of Korean medicine theory and contribute to its development by generating biologically plausible hypothesis.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.11a
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• pp.165-169
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• 1996

The cytochrome P450 (P450) proteins have been studied extensively because of their prominent roles as catalysts in the oxidations of drugs, carcinogens, steroids, alkaloids, vitamins, and other important chemicals (Guengerich, 1991). In the past decade the study of these enzymes has been advanced by the cloning of cDNAs and expression of the proteins in several heterologous vector systems. One approach that has been employed in this and other laboratories is expression in bacteria. To date at least 31 different mammalian P450s have been expressed in Escherichia coli-band systems (Guengerich et al., 1996). In most of these cases the N-terminus has been altered to facilitate better expression (Barnes et al., 1991).

• Biomolecules & Therapeutics
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• v.9 no.1
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• pp.63-68
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• 2001

General pharmacological properties of (R)-JG-381 were examined in laboratory animals to investigate its safety profile. Administration of (R)-JG-381 (50 and 100 mg/kg) in mice and rats had no effects of general behaviors, central nervous system of the animals in test systems of pentobarbital-induced sleeping time, writhing syndromes induced by 0.7% acetic acid, chemo-shock produced by pentylenetetrazole, and, however, had mild effects on motor coordination. Heart rate and blood pressure were not changed by (R)-JG-381 treatment. (R)-JG-381 also showed mild effects on intestinal propulsion and gastric secretion. These results suggest that (R)-JG-381 dose not exert serious pharmacological effects.