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류승렬(Seung Rel Ryu),김혜진(Hye Jin Kim),홍진태(Jin Tae Hong),이종권(Jong Kwon Lee),이선희(Sun Hee Lee),이병무(Byung Mu Lee),김부영(Pu Young Kim) 대한약학회 1999 약학회지 Vol.43 No.5
Abuse liability of ephedrine was investigated by measurement of locomotor activity and self-administration in Sprague-Dawley rats. Locomotor activity was determined in rats treated with 3, 10 and 30mg/kg ephedrine for 14 days. Self-administration by ephedrine (0.23, 1 and 2.3mg/kg) was examined in food-trained rats. We also examined effect of dopamine receptor antagonist (spiperone, 30mcg/kg) on the ephedrine-induced response of self-administration. Body weight was not statistically difference between control and ephedrine treatment group, but locomotor activity was dose-dependently increased. Self-administration for ephedrine was decreased in the early response (day 1 and 2) but the response was increased by higher dose of ephedrine. Self-administration was decreased by dopamine receptor antagonist (spiperone). These data showed that ephedrine increased locomotor activity and induced response of self-administration, and the effects of ephedrine were partially related to the dopaminergic system, which suggest that ephedrine may have abuse liability.
류승렬,김혜진,홍진태,김대병,박훈,이종권,김윤정,김미정,이은희,이선희,김부영 식품의약품안전청 1998 식품의약품안전청 연보 Vol.2 No.-
에페드린은 구조적으로(+)methamphetamine과 유사할 뿐만 아니라 중추신경흥분작용이 있는 물질로 알려져 있으며 미국 등ㅇ서 오남용으로인한 부작용이 보고되어 있어 동물모델을 이용하여 기존에 알려져(+)methamphetamine과 에페드린에 대한 자발운동량 및 자가섭취능을 측정하여 의존성여부를 검색하였다.Sprague-Dawley랫드에 에페드린(3,10 및 30mg/kg)을 2주간 투여하여 이들 약물에의한 임상관찰, 체중변화와 자발운동량을 측정하여 약물에 대한 직접적인 독성현상과 행동양상을 관찰하였다. 또한 자가섭취능 실험을 위해 랫드를 1주일간 일정한 양(20g/day)의 사료를 섭취시켜 먹이에 의한 학습을 유도한 후 (+)methamphetamine(0.1mg/kg) 및 에페드린(0.23, 1 및 2.3mg/kg)에 의한 자가섭취능과,(+)methamphetamine에 의해 학습된 랫드를 이용하여 (+)methamphetamine과 2.3mg/kg에페드린에 으하 ㄴ자가섭취능의 강화효과 변화를 관찰하고, 자가섭취능 작용기전이 dopaminergic system과 관련이 있는지를 알아보기 위해 dopamine receptor antagonist인 spiperone (30μg/kg)을 처리하여 에페드린 자가섭취능이 dopaminergic effect와 연관성이 있는지를 연구하엿다. 그 결과 에페드린에 으힌 채중의 변화는 나타나지 않앗으나, 용량-의존적을 자발운동량을 증가시켰다. 또한 에페드린은 먹이로 유도된 학습반응을 감소시켰으며,에페드린 투여 중단에 의한 자가섭취를 유지하려는 강황효고ㅓㅏ를 증가시켰다. 고용량에서 이와 같은 영향은 더욱 컸으며, dopamine receptor antagonist인 spiperone에 으해서는 자가섭취능이 감소하였다. 본 실험결과 에페드린은 쟈밭운동량을 중가시키고, 자가섭취능 강화효과가 잇으며 이 효과는 dopamine receptor와 관련되어 나타나는 것으로 싸료되어 추후 작용기전 및 다른 의존성여부 확인실험을 통해 에페드린의 의존성 여부를 밝히는 실험이 필요하다고 판다뇐다. We studita whether ephedrine has physical dependent effect since it hds been found to be a central nervous system stimulant. aBd is structually similar to methamphetamine. Dependence wasevaluated by measuremerㄴt of locomotor activity and setf-administration in Sprague-Bawler rats. Bodyweight and locomotor activity were determined in rats treated with 3, 10 and 30mg/11g (-)ephrdrinefor 14 days. Self~administration by ephedrine (0.23, 1 and 2.3mg/kg) was examined in food-trained rats.We also examined effect of dopamine receptor antagonist (spiperone, 30 rg/kg) on the ephedrine-in-duced response of self-administration. Body weight was not statistically difference between control andephedrine treatment group. Locomotor activity was increased by ephedrine in a dose-dependence pat-tern. Ephedrine decreased the response of self-administration in foed-trained rats and increased rein-forcing response of self-administration for 3 days after stop tlle treatment. This reinforcing effect wasincreased by higher dose of ephedrine, and decreased by dopamine receptor antagonist spiperone. Thesedata shewing ephedrine increased locomotor activity and induced reinforciBg effort of self-administration, and the reinforcing effect of ephedrine was parl.ially related to the dopaminergic system.suggest fat ephedrine may have physical dependence.
Involvement of Cortical Damage in the Ischemia/Reperfusion-Induced Memory Impairment of Wistar Rats
Hong, Jin-Tae,Ryu, Seung-Rel,Kim, Hye-Jin,Lee, Sun-Hee,Lee, Byung-Moo,Kim, Pu-Young The Pharmaceutical Society of Korea 2000 Archives of Pharmacal Research Vol.23 No.4
The effect of ischemia/reperfusion-induced neuronal damage on the memory impairment were investigated using active avoidance and Morris water maze tasks in Wistar rats. Focal ischemia was induced by 1 h occlusion of the right middle cerebral artery (MCA) of Wistar male rats. Reperfusion was induced by releasing the occlusion and restoring the blood circulation for 24 h. The acquisition and preservation memory tested by active avoidance showed a significant difference between the sham and ischemia/reperfusion group. The water maze acquisition performance was also significant difference between sham and ischemia/repefusion groups in both latency and moving distance. The infarction volume was increased by the ischemia/reperfusion. Furthermore, the cresyl violet staining of the ischemia/reperfusion brain showed severe neuronal damage (pyramidal cell loss) in the cortex in addition to the striatum lesion of brain. This study shows that pyramidal cell damage in the cortex lesion may be partially related to memorial disturbance in the ischemia/reperfusion brain injury.
In vitro Alternatives to Skin Irritation Test
Kim, Dai Byung,Ryu, Seung Rel,Kim, Pu Young,Shin, Dae Sup,Lee, Sun Hee,Koh, Jae Sook,Park, Won Sae 한국응용약물학회 1995 Biomolecules & Therapeutics(구 응용약물학회지) Vol.3 No.3
In vitro cell culture system has been proposed as a promising alternative model to in vivo skin irritation test. These studies were performed to screen the cytotoxicity effects of surfactants using normal human skin fibroblasts. Cell membrane integrity assessed by the leakage of lactate dehydrogenase (LDH) and mitochondrial integrity by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] reduction test were affected in a dose dependent manner. The irritation potential of surfactants to human skin patch test, and the changes of capillary permeability by rabbit intradermal safety test were assessed as in vivo methods. Our results suggest that LDH leakage assay and MTT reduction test using cultured human fibroblasts could be predictive for the irritancy of various surfactants in human, and LDH assay is superior correlated with in vivo test (r=0.886) to MTT test with in vivo test (r=0.757).