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장춘곤,강문규,Jae-Han Cho,Sun-Bok Lee,Hyuntaek Kim,박순권,Jinwoo Lee,박성규,Moochang Hong,Min Kyu Shin,심인섭,배현수 대한약학회 2004 Archives of Pharmacal Research Vol.27 No.10
Depression is associated with a dysfunctional serotonin (5-hydroxytryptamine; 5-HT) system. More recently, several lines of evidence suggest that an important factor in the development of depression may be a deficit in the function and expression of $5-HT_{1A}$ receptors. The present study assessed if Nelumbinis Semen (N. s.) had an anti-depression effect through reversing a decrease in $5-HT_{1A}$receptor binding in rats with depression-like symptoms induced by chronic mild stress. Using a $5-HT_{1A}$ receptor binding assay, with a specific $5-HT_{1A}$receptor agonist, 8- OH-DPAT (8-hydroxy-2-(di-n-propylamino) tetralin), the mechanism of the anti-depression effect of N. s. on rats was investigated, and the effects compared with two well-known antidepressants, Hyperium Perforatum (St. Johns Wort) and fluoxetine (Prozac). Animals were divided into five groups: the normal (N) group without chronic mild stress (CMS), the control (C) group under CMS for 8 weeks, the Nelumbinis Semen (N. s.) treatment group under CMS for 8 weeks, the Hyperium Perforatum (H. p.) treatment group under CMS for 8 weeks and finally, the fluoxetine (F) treatment group under CMS for 8 weeks. Each treatment was administered to rats during the last 4 weeks of the 8-week CMS. A sucrose intake test was performed to test the anti-depression effect of N. s. The N. s. treatment significantly reversed the decreased sucrose intake under CMS (P<0.05 compared to control group under CMS). In the CA2 and CA3 regions of the hippocampus, both N. s. and H. p. reversed the CMS-induced decrease in $5-HT_{1A}$receptor binding. In the I to II regions of the frontal cortex, N. s. and H. p. also reversed the CMS-induced decrease in$5-HT_{1A}$receptor binding, and even showed a significant increase in $5-HT_{1A}$receptor binding compared to the F treatment group (N. s. vs. P, p<0.05, H. p. vs. P, p<0.05). However, in the hypothalamus, all treatments reversed the CMSinduced decrease in $5-HT_{1A}$receptor binding. This reversal effect of N. s. on the decrease in $5-HT_{1A}$receptor binding in the frontal cortex, hippocampus and hypothalamus of rat brains was very similar to that of H. p, but different from that of F. It is concluded that N. s. presents an anti-depression effect through enhancing $5-HT_{1A}$receptor binding.
Jang, Choon-Gon,Kang, Moonkyu,Cho, Jae-Han,Lee, Sun-Bok,Kim, Hyuntaek,Park, Soonkwon,Lee, Jinwoo,Park, Seong-Kyu,Hong, Moochang,Shin, Min Kyu,Shim, In-Sup,Bae, Hyunsu WHO COLLABORATING CENTRE FOR TRADITIONAL MEDICINE 2004 東西醫學硏究所 論文集 Vol.2004 No.-
Depression is associated with a dysfunctional serotonin (5-hydroxytryptamine; 5-HT) system. More recently, several lines of evidence suggest that an important factor in the development of depression may be a deficit in the function and expression of 5-HT_(1A) receptors. The present study assessed if Nelumbinis Semen (N. s.) had an anti-depression effect through reversing a decrease in 5-HT_(1A) receptor binding in rats with depression-like symptoms induced by chronic mild stress. Using a 5-HT_(1A) receptor binding assay, with a specific 5-HT_(1A) receptor agonist, 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino) tetralin), the mechanism of the anti-depression effect of N. s. on rats was investigated, and the effects compared with two well-known antidepressants, Hyperium Perforatum (St. Johns Wort) and fluoxetine (Prozac). Animals were divided into live groups: the normal (N) group without chronic mild stress (CMS), the control (C) group under CMS for 8 weeks, the Nelumbinis Semen (N. s.) treatment group under CMS for 8 weeks, the Hyperium Perforatum (H. p.) treatment group under CMS for 8 weeks and finally, the fluoxetine (F) treatment group under CMS for 8 weeks. Each treatment was administered to rats during the last 4 weeks of the 8-week CMS. A sucrose intake test was performed to test the anti-depression effect of N. s. The N. s. treatment significantly reversed the decreased sucrose intake under CMS (P<0.05 compared to control group under CMS). In the CA2 and CA3 regions of the hippocampus, both N. s. and H. p. reversed the CMS-induced decrease in 5-HT_(1A) receptor binding. In the Ⅰ to II regions of the frontal cortex, N. s. and H. p. also reversed the CMS-induced decrease in 5-HT_(1A) receptor binding, and even showed a significant increase in 5-HT_(1A) receptor binding compared to the F treatment group (N. s. vs. P₁ p<0.05, H. p. vs. P₁ p<0.05). However, in the hypothalamus, all treatments reversed the CMS-induced decrease in 5-HT_(1A) receptor binding. This reversal effect of N. s. on the decrease in 5-HT_(1A) receptor binding in the frontal cortex, hippocampus and hypothalamus of rat brains was very similar to that of H. p, but different from that of F. It is concluded that N. s. presents an anti-depression effect through enhancing 5-HT_(1A) receptor binding.
Tyrosine Kinase is Involves in Hemin-Induced Pyresis
이상호,장춘곤,이석용 대한약학회 2003 Archives of Pharmacal Research Vol.26 No.5
To investigate the mechanisms involved in hemin-induced febrile response, the rectal temperature of rats were measured after intracerebroventricular (i.c.v.) injections of hemin, with or without antagonists. Hemin (10 mg) elicited a significant febrile response, which lasted from 30 min, to more than 6 h, after its administration, but this was not the case with biliverdin (i.c.v.) and bilirubin (i.c.v.). The hemin-induced febrile response was significantly inhibited by pretreatment with an inhibitor of tyrosine kinase (genistein), but not by pretreatment with an inhibitor of protein kinase C (chelerythrine) and a scavenger of iron (deferoxamine). These results suggest that tyrosine kinase is involved in the hemin-induced febrile response.
Acarbose 제제의 약력학적 평가 및 생물학적동등성 시험법에 대한 연구
배정우,장춘곤,이석용,Bae, Jung-Woo,Jang, Choon-Gon,Lee, Seok-Yong 대한약학회 2007 약학회지 Vol.51 No.6
Arcabose is a competitive inhibitor of the intestinal ${\alpha}$-glucosidases and reduces the postprandial digestion and absorption of carbohydrate and disaccharides. Due to its negligible oral absorption, measuring drug concentration in the plasma is impractical. Thus, the common pharmacokinetic study is not available to determine the bioequivalence of the generic acarbose preparations. The aim of this study is the establishment of pharmacodynamic assessment method for the bioequivalence test of the generic acarbose preparations. Placebo-controlled cross-over ($3{\times}3$) clinical study was conducted in 23 healthy volunteers. Volunteers received a single oral dose of placebo, reference drug ($Glucoby^{(R)}$ 100 mg, Lot # D043) or test drug ($Glucoby^{(R)}$ 100 mg, Lot # E005) just before breakfast, then blood samples for evaluation of serum glucose and insulin levels were taken during for 4 hours. $C_{max},\;AUC_{0-2},\;AUC_{0-4},\;{\Delta}C_{max},\;{\Delta}AUC_{0-2}\;and\;{\Delta}AUC_{0-4}$ of the postprandial plasma glucose level significantly decreased when a single dose of acarbose 100 mg preparations was administered. However, any significant difference was not detected between the groups taken the reference drug and the test drug. These results proposed that the pharmacodynamic protocols of this study is suitable to use for bioequivalence test of acarbose preparations. On the basis of the results of this study and the data of literature on this subject, the standard protocols of bioequivalence study of acarbose preparation are proposed.
Effect of CYP2C9*3 Allele on the Pharmacokinetics of Naproxen in Korean Subjects
배정우,김지홍,장춘곤,박영서,이석용,최창익,김미정,김형지,변성애,창영순 대한약학회 2009 Archives of Pharmacal Research Vol.32 No.2
The genetically polymorphic CYP2C9 metabolizes many non-steroidal anti-inflammatory agents, including naproxen. This study examined the effects of a CYP2C9 genetic polymorphism on the pharmacokinetics of naproxen in Korean subjects. Twenty healthy male subjects carrying a CYP2C9*1/*1 (n=14) or CYP2C9*1/*3 (n=6) polymorphism were enrolled. After a single-dose of 275 mg naproxen Na, blood samples were collected at various times over a 72 h period and the plasma naproxen concentration was measured. The plasma concentration of naproxen was determined by HPLC analysis with UV detection, and the pharmacokinetic parameters were calculated. The mean plasma concentrationtime profiles of naproxen in the CYP2C9*1/*3 and CYP2C9*1/*1 individuals were similar. There were no significant differences in the pharmacokinetics of naproxen between CYP2C9*1/*1 and CYP2C9*1/ *3 genotypes. The AUC0-∞ (p = 0.759) and oral clearance (p = 0.823) of naproxen were also similar in individuals with CYP2C9*1/*3 and CYP2C9*1/*1. Overall, a genetic polymorphism of CYP2C9 does not significantly affect the pharmacokinetics of naproxen. Therefore, naproxen does not require a dose adjustment for individuals with the CYP2C9*1/*3 genotype.