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내성 및 의존성 형성 약물의 약효 검색

  • 김학성;오기완
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1993.04a
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    • pp.77-77
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    • 1993
  • 약물 내성 (tolerance) 및 의존성 (dependence)은 그 약물이 지니고 있는 여러 가지 약리작용과 관련되어 형성된다. 약물의 반복투여 후, 나타나는 작용이 처음의 반응 (response) 보다 감소되어 나타나는 현상 즉, 내성과, 이와는 반대로 약물반복 투여 후 나타나는 작용이 처음의 반응보다 점점 증가하는 역내성 (reverse tolerance 또는 sensitization) 측정에 있어서 약물에 따라 적절한 검색 방법을 설명한다. 의존성에 있어서 약물 섭취 결과 mood가 변하거나 도취감 또는 만족감을 일으키게 되면 그 감각을 재 경험하고 싶다는 욕구가 일어나게 되는 정신적 의존성(psychic dependence)과, 약물을 반복 투여하다가 갑자기 투여를 중단 했을때 여러가지 생리학적인 또는 행동적인 변화가 급격히 증가하여 금단증상을 나타내는 신체적 의존성 (physical dependence) 측정 방법을 제시한다. 내성과 의존성은 근본적으로 다르지만 대부분의 경우 내성이 형성되면 의존성이 형성된다. 여기서는 주로 morphine과 psychostimulants를 투여한 후 나타나는 약리작용에 대한 내성과 opioids (마약성 진통제)의 의존성 평가 방법에 대한 model을 설명하고자 한다 진통성 내성(analgesic tolerance)에 있어서 진통제의 진통력은 진통력 측정 방법(tail pinch, paw-withdrawal, tail flick, tail-withdrawal, hot plate, writhing, etc)에 따라 차이가 있기 때문에 각각의 진통제의 정합한 내성 측정 방법을 결정할 필요가 있다. 역내성 (roversetolerance)은 cocaine, amphetamine, opioids둥의 만성투여에서 일어난다. 이들 역내성을 측정하는 한 방법으로 자발운동을 측정하는데 locomotor activity cage나 tilting cage를 이용한다. 정신적 의존성(psychic dependence)은 약물 섭취 욕구를 이용한 CPP (conditioned place preference)법을 소개한다. 신체적 의존성 (physical dependence)은 opioids를 만성적으로 투여한 후 naloxone으로 precipitation하여 나타난 여러 가지 금단증상을 측정하고 몇몇 평가 model을 제시한다.

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The Effects of Betula Platyphylla on Cartilage Pratection, Anti-inflammatory and Analgesic Activity in Arthritis (관절염 유발 모델에서 화피가 연골 보호 및 소염 진통에 미치는 영향)

  • Kim, Yeo-Jin;Lee, Jae-Dong;Lee, Yun-Ho
    • Journal of Acupuncture Research
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    • v.24 no.2
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    • pp.73-81
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    • 2007
  • 목적 : 본 연구는 화피의 연골 보호 및 소염 진통 작용을 알아보고, 화피를 이용한 관절염치료 약침액 개발의 기초자료를 얻기 위해 고안되었다. 방법 : In vitro에서는 토끼 무릎관절에서 배양된 연골조직에 5ng/ml IL-1${\alpha}$ 처리 후, 화피의 연골보호 효과, 연골세포에 대한 독성을 조사하였다. In vivo에서는 토끼 무릎관절내 collagenase를 주입, CIA 유발 후, 28일간 매일 토끼의 구강으로 화피, 증류수, CEX를 투여하였으며, 연골보호, 소염, 진통에 대한 측정을 하였다. 결과 : 화피는 proteoglican 및 collagen분해 억제, MMPs 활성 억제로 연골 보호 효과가 있었으며, 연골 세포에 대한 독성이 없었다. 소염작용은 PGE2 생산 억제 및 COX-2발현 억제, carrageenan 유발 쥐 모델에서의 부종 억제로 확인되었다. 진통작용은 tail flick test에서의 latency time 증가, formalin test에서의 염증성 통증억제로 나타났다. 결론 : 화피가 퇴행성관절염에 대한 연골 보호 효과 및 소염 진통 작용이 있으므로, 이를 근거로 약침액을 개발 응용하면 퇴행성관절염 치료에 활용될 수 있다고 사료된다.

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Inhibitory Effect of Ginseng Total Saponins on the DEvelopement of Tolerance to U-50,488H-Induced Antinociception is Dependent on Serotonergic Mechanisms (U-50,488H 진통성 내성형성에 대한 인삼 사포닌의 억제효과는 Serotonin 기전에 의존적이다)

  • Kim, Hack-Seang;Rhee, Gyu-Seek;Oh, Ki-Wan
    • Journal of Ginseng Research
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    • v.19 no.3
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    • pp.202-205
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    • 1995
  • We have previously reported that the antagonism of U-50,488H-induced antinociception in mice pretreated with ginseng total saponins (GTS) Ivas abolished by pretreatment with a serotonin precursor, 5-hydroxytryptophan (5-HTP), but not by a noradrenaline precursor, L-dihydroxyphenylalanine (L-DOPA) in the tail flick test. In the present experiments, the effect of the same GTS on the development of tolerance to U-50,488H-induced antinociception was determined. GTS inhibited the development of tolerance to U-50,488H-induced antinociception. The inhibitory effect of GTS on the development of tolerance to U-50,488H-induced antinociception was reversed by 5-HTP, but not by L-DOPA. These findings suggest that the inhibitory effect of GTS on the development of tolerance to U-50,488H-induced antinociception is dependent on serotonergic mechanisms. Key words Ginseng total saponin, U-50,488H, tolerance, serotonin.

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A Saponin Complex, KPRG-C, and Its Sapogenin Complex, KPRG-D, Reduce Nociception and Inflammation in Animals

  • Nam, Jung-Hwan;Jung, Hyun-Ju;Choi, Jong-Won;Park, Hee-Juhn
    • Korean Journal of Plant Resources
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    • v.20 no.3
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    • pp.226-233
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    • 2007
  • To develop a clinically available saponin- or sapogenin complex from Oriental medicines, the EtOH extract (KPRG-A) was obtained by extracting from the four crude drugs, Kalopanacis Cortex, Platycodi Radix, Rubi Fructus and Glycyrrhizae Radis. The BuOH fraction (KPRG-B), a crude saponin complex, was prepared by fractionating KPRG-A, which were further completely hydrolyzed to afford the sapogenin complex (KPRG-D). In an attempt to find the antinoicpetive effects of the saponin complex and sapogenin complex, KPRG-C, and -D, were assayed by writhing-, hot plate-, and tail-flick tests using mice or rats. The three samples were also subjected to antiiflammatory tests using serotonin-induced and carrageenan-induced hind paw edema mice and rats, respectively. The three samples significantly reduced inflammations and pains of the experimental animal. The potency were found in the order of KPRG-D> KPRG-C> KPRG-B. The most active sample, KPRG-D, caused no death, no body increase or no anatomical pathlogic change even at 2,000 mg/kg dose. These results suggest that a sapogenin complex, KPRG-D, which was found to contain mainly hederagenin, platycodigenin, polygalacic acid, 23-hydroxytormentic acid, glycyrrhetic acid together with minor triterpene acids, could be a potential candidate for antiinflammatory therapeutics.

Effects of Panax Ginseng on the Development of Morphine Induced Tolerance and Dependence(III) -Effects of Protopanaxadiol Fraction and Prtopanaxatriol Fraction in Mice- (모르핀의 내성 및 의존성 형성에 미치는 인삼의 효과(III) -인삼의 Protopanaxadiol 분획 및 Protopanaxatriol 분획의 영향-)

  • 김학성;오세관;최강주;이해빈
    • YAKHAK HOEJI
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    • v.29 no.4
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    • pp.188-192
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    • 1985
  • Protopanaxadiol (PD) fraction and protopanaxatriol (PT) fraction were separated from thebutanol fraction of panax ginseng roots. Each group of mice was injected with morphine hydrochloride (40 mg/kg s.c.) three times at 8 hr intervals for a period of 6 days. PD fraction and PT fraction were injected (25, 100 mg/kg i.p.) to mice 1 hr prior to the third morphine injection daily. Inhibition of morphine tolerance was evidenced by the increase in analgesic response to morphine hydrochloride (10mg/ kg i.p.) as estimated by the tail flick method. Inhibition of morphine tolerance by PT fraction was effective but there was no remarkable difference in inhibition of tolerance development between control group andPD fraction group.

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Effects of Ginseng Total Saponin on Stress-Induced Analgesia (스트레스로 유도된 진통력에 미치는 인삼의 효과)

  • Kim, Hack-Seang;Chung, Myeon-Woo;Jang, Choon-Gon;Park, Woo-Kyu;Oh, Ki-Wan
    • Journal of Ginseng Research
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    • v.17 no.1
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    • pp.22-28
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    • 1993
  • This study was undertaken to determine the effects of ginseng total saponin (GTS) on stress- induced analgesia (SIA) in mice. intermittent foot shock (FS)-SIA was antagonized not by on but by naloxone in the tail flick FS-SIA which was not antagonized by naloxone in the T.F. test. On the other hand, GTS did not antagonize the continuous FS-SIA naloxone antagonized in the T.P. test. Also GTS antagonized psychological (PSIF)-SIA which was not antagonized by naloxone in the T.F. test. However, GTS did not antagonize the PSY-SIA which naloxone antagonized in the T.P. test. Forced swimming (FSIP)-SIA was not affected by both GTS and naloxone. These results suggest that the antapeonisms of intermittent FS-SIA in the T.F. test, continuous FS-SIA and PSY-SIA by GTS are mediated by non-opioid mechanisms but the antagonism of intermittent FS-SIA in the T.P. test by GTS is mediated by opioid mechanism.

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A Study on the Interline Flicker Reduction of Teletext by using KProgressive Scan (점진적 주사방식에 의한 문자 방송에서의 라인 떨림 감소에 관한 연구)

  • Kim, Jae-Sun;Song, Chul
    • The Journal of Korean Institute of Communications and Information Sciences
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    • v.17 no.9
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    • pp.982-992
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    • 1992
  • We developed the interface system between D-SCAN TV system and the Teletext system to reduce the effect of interline flick. At first, horizontal and vertical signal is separated from the composite signal. The stable vertical sync and horizontal sync is applied to the conventional Teletext system and the its output has R.G.B signal form and the output of the Teletext system. This signal is converted into composite signal and is switched at the video selector system in TV to process the signal by progressive method.

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Skin Penetration and in Vivo Local Anesthetic Effect of Microemulsion-based Hydrogels Containing Lidocaine (리도카인을 함유하는 마이크로에멀젼 겔의 피부침투성 및 in vivo 마취효과)

  • Shin, Hyun-Woo;Lee, Gi-Bong;Lee, Sang-Kil;Choi, Young-Wook
    • Journal of Pharmaceutical Investigation
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    • v.30 no.4
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    • pp.273-278
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    • 2000
  • Several topical preparations containing lidocaine, a widely used local anesthetic agent, have been developed and marketed recently for the treatment of premature ejaculation. In this study, microemulsion(ME)-based hydrogels containing lidocaine were prepared by dispersing ME to hydrogel bases such as Carbopol, sod. alginate, and sod. carboxymethylcellulose. Lidocaine-containing ME was thermodynamically stable over 6 months and had a diameter ranging from 10 to 100 nm. In vitro skin penetration of lidocaine from ME-based hydrogels followed apparent zero-order kinetics. ME-based hydrogel showed higher drug penetration during fifteen minutes after application than alcoholic hydrogel, reference preparation. Tail flick test in rat was introduced to compare in vivo local anesthetic effects of different hydrogels, and the results showed that ME-based hydrogels are superior to other hydrogels. In optical microscopy, recrystallization of lidocaine was observed within 5 min after application of reference hydrogel, but there was no change in ME-based hydrogels even after 30 minnute. These results indicated that ME-based hydrogels had some advantages in skin penetration, anesthetic effect and physical stability compared with alcoholic hydrogels. Finally it is possible to conclude that ME-based hydrogels containing lidocaine is a good topical drug delivery system for the treatment of premature ejaculation.

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Electroacupuncture Analgesia Is Improved by Adenoviral Gene Transfer of Dopamine Beta-hydroxylase into the Hypothalamus of Rats

  • Kim, Soo-Jeong;Chung, Eun Sook;Lee, Jun-Ho;Lee, Chang Hoon;Kim, Sun Kwang;Lee, Hye-Jung;Bae, Hyunsu
    • The Korean Journal of Physiology and Pharmacology
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    • v.17 no.6
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    • pp.505-510
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    • 2013
  • Electroacupuncture (EA) is a modified form of acupuncture that utilizes electrical stimulation. We previously showed that EA stimulated rats were divided into responders that were sensitive to EA and non-responders that were insensitive to EA based on the tail flick latency (TFL) test. The dopamine beta-hydroxylase (DBH) gene was more abundantly expressed in the hypothalamus of responder rats than non-responder rats. To determine whether overexpression of DBH gene expression in the hypothalamus modulate EA analgesia, we constructed a DBH encoding adenovirus and which was then injected into the hypothalamus of SD rats. Microinjection of DBH or control GFP virus into the hypothalamus had no changes on the basal pain threshold measured by a TFL test without EA treatment. However, the analgesic effect of EA was significantly enhanced from seven days after microinjection of the DBH virus, but not after injection of the control GFP virus. DBH expression was significantly higher in the hypothalamus of DBH virus injected rat than control GFP virus or PBS injected rats. Moreover, expression of the DBH gene did not affect the body core temperature, body weight, motor function or learning and memory ability. Although the functional role of DBH in the hypothalamus in the analgesic effect of EA remains unclear, our findings suggest that expression of the DBH gene in the hypothalamus promotes EA analgesia without obvious side-effects.

Analgesic Effect of Clematidis Radix (CR) Herbal-acupuncture on the Test Rats with Induced Acute Pain (급성통증 유발 흰쥐에 대한 위령선약침(威靈仙藥鍼)의 통증 억제효과)

  • Choi, Won-Joo;Kim, Ki-Bong;Kim, Kyung-Ho;Kim, Jang-Hyun
    • Journal of Acupuncture Research
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    • v.26 no.6
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    • pp.91-100
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    • 2009
  • Objectives : The objective of this study is to investigate Anti-nociceptive and anti-inflammatory effects of Clematidis Radix (CR) herbal-acupuncture on the test rats with induced acute pain. Methods : The effects of Clematidis Radix (CR)-distillates were investigated in three types of models with three different pain. Highly purified distillate of CR called CR herbal-acupuncture was injected to Zusanli ($ST_{36}$) acupoint. In the tail flick test, the CR herbal-acupuncture treatment did not show a significant effect of relieving acute pain. To investigate the anti-inflammatory effect of CR herbal-acupuncture, the second testing model'pain was induced by injecting formalin to its planter. For the last model, carrageenan was injected into tarsal joint. the medicinal effect of CR herbal-acupuncture was evaluated through the behavioral analyses such as licking time, weight distribution ratio and ankle circumference. Results : In the formalin test, the analgesic effect of CR herbal-acupuncture was more pronounced in the late phase (for 20 min after the early phase) than in the early phase (for the first 10 min post formalin injection). It was proven by weight distribution ratio testing and ankle edema testing that herbal-acupuncture of CR inhibited arthritis caused by the carrageenan. Conclusions : These results revealed that CR herbal-acupuncture was effective to alleviate the inflammatory pain and could be used as an analgesic treatment with an anti-inflammatory effect.

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