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Nortriptyline이 가토 혈중 주정농도에 미치는 영향에 관한 실험적 연구

Title
 Nortriptyline이 가토 혈중 주정농도에 미치는 영향에 관한 실험적 연구 
Other Titles
 Effects of nortriptyline on blood alcohol level in rabbits 
Issue Date
1977
Publisher
 연세대학교 대학원 
Description
의학과/석사
Abstract
[한글]Sulser 등은 1962년 최초로 amitriptyline의 항우울작용이 그의 대사산물인 desmethylamitriptyline 즉 nortriptyline의 중개에 의함을 발표한 이후 nortriptyline이 내인성 우울에 저효함이 다수의 연구결과 밝혀졌으며 경구반복투여로 일정상태 혈장농도가 유지된 다는 사실에 입각하여 그의 kinetios에 대한 연구가 활발해진 항우울제이다. 한편 정은제 및 항우울제의 복용시 주정섭취로 인한 사고유발 위험성이 증가하고 있다. 특히 우울증과 음주벽 간에 밀접한 관계가 있으며, 최근 다수의 항우울제가 가토 혈중 주정농도를 증가 시킨다는 실험보고가 있어, 항우울제중의 하나인 nortriptyline이 가토 혈중 주정농도에 미치는 영향에 관한 연구는 이론적으로나 실제적으로 흥미있는 바 있어 실험적으로 연구하여 보았다. 실험재료 및 방법 1. 실험동물은 체중 2.0 kg 내외의 성숙 자웅가토를 사용하였다. 2. 비교군에서는 주정만 단독 투여하였다. 3. 실험군은 경구투여 용량과 주정농도와와 관계를 비교해보기 위해 nortriptyline을 체중 매 kg당 10 mg 및 20 mg씩 각각 일정한 시각에 투여했고, 최종투여는 주정투여 1시간 30분 전에 시행하였으며, 한편 경구투여 일자와 주정농도와의 관계를 비교 해보기 위해 각각 5일 및 10일간씩 투여하였다. 4. 주정투여는 20 % ethanol용액을 체중 매kg당 5.0 ml를 이변정맥 내로 5분간에 걸쳐 서서히 정맥주사하였다. 5. 체혈은 주정투여후 15분과 45분에 심장천자로 시행하였다. 6. 주정의 혈중농도는 Cavett씨 방법에 의해 측정하였다. 실험성적 1. Nortriptyline을 10 mg/kg씩 연5일 및 연10일간 투여시 주정투여후 15분 및 45분 각각에서 모두 혈중 주정농도에 유의한 변화가 없었다. 2. Nortriptyline을 20 mg/kg씩 연5일 및 연10일간 투여시 주정투여후 15분 및 45분 각각에서 모두 혈중 주정농도를 유의하게 증가시켰지만, 연5일과 연10일 투여 간의 비교에서는 유의한 차이가 없었다. 이러한 실험성적은 nortriptylinedml 작용발현에는 일정수준의 혈장농도가 필요함을 암시하며 그 수준에 도달하면 혈중 주정농도를 증가시키나 투여일자와는 무관함을 보여준 결과라고 볼 수 있다. 혈중 주정농도를 상승시키는 정확한 기전은 알 수 없으나 증가된 혈준 catecholamine이 유리지방산을 증가시켜 ADH작용을 억제하는 기전이 가장 유력한 것으로 추측된다.
[영문]In 1962, Sulser et al. first demonstrated that the antidepressant action of amitriptyline is mediated through a metabolic product, desmethylamitriptyline (nortriptyline). And nortriptylino was synthesized by Dr. H. Spiegelberg and Dr. G. Rey-Bellet. Thereafter numerous studies have indicated that nortriptyline is effective in the endogenous depression. Since Hammer et al., in 1967, found that an apparent steady-state plasma level is achieved by repetitive oral administration of nortriptyline at fixed intervals, the enormous studies of the metabolism of nortriptyline have been done. Alexanderson et al., in 1969, performed the pharmacokinetic studies with nortiptyline in 78 twins, and it is found that nortriptyline kinetics in man is under the polygenic control. Lawton and Cahn had suggested that any new psychotropic drugs should be tested for its interaction with alcohol, because they had been shown to increase the dangers of consuming alcoholic beverage. Recently it has been reported that various psychotropic and antidepressant drugs elevated the blood alcohol level in rabbits. In view of these reports, the author conducted an animal experiment to investigate the effects of nortriptyline on blood alcohol level in rabbits. Material and Method 1. The experimental work was done on mature rabbits of both sexes, weighing about 2.0 kg. 2. The experimental animals were divided into 2 groups; the control and the experimental group. 3. The control group was given alcohol alone. 4. The experimental group was divided into 2 subgroups; a) alcohol plus nortriptyline, 10 mg/kg of body weight, and b) alcohol plus nortriptyline, 20 mg/kgof body weight group. 5. Each alcohol plus nortriptyline group was further divided into 2 subgroups in which one subgroup was given nortriptyline for 5 days and another for 10 days. 6. Nortriptyline was orally given in a single dose at a fixed time. The last dose was given one hour and a half before alcohol administration. 7. In all groups 20% ethanol solution was slowly given in a dose of 5.0 ml/kg of body weight in 5 minutes by intravenous route. 8. All of the blood specimens were obtained by cardiac puncture at 15 and 45 minutes after alcohol administration. 9. The blood alcohol level determination was made by Cavett's method. Results 1. Alcohol plus nortriptyline, 10 mg/kg of body weight for 5 days. Nortriptyline did not change the blood alcohol level significantly at both 15 and 45 minutes after alcohol administration (P>0.4). 2. Alcohol plus nortriptyline, 10 mg/kg of body weight for 10 days. In this group, there was also no significant change in the blood alcohol level at both 15 and 45 minutes after alcohol administration (P>0.4). 3. Alcohol plus notriptyline, 20 mg/kg of body weight for 5 days. In this group, Nortriptyline elevated the blood alcohol level significantly at both 15 and 45 minutes after alcohol administration (P<0.01). 4. Alcohol plus nortriptyline, 20 mg/kg of body weight for 10 days. In this group, nortriptyline elevated also the blood alcohol level significantly at both 15 and 45 minutes after alcohol administration (P<0.01). 5. The blood alcohol level of nortriptyline 20 mg/kg of body weight for 5 days was a little higher than that of nortriptyline for 10 days, but the difference was not significant statistically at both 15 and 45 minutes after alcohol administration (P>0.3). Conclusions 1. Nortriptyline when administered orally in a dose of 10 mg/kg of body weight daily for 5 or 10 days, did not elevate the blood alcohol level significantly at both 15 and 45 minutes after alcohol administration. 2. Nortriptyline when administered orally in a dose of 20 mg/kg of body weght daily for 5 or 10 days, elevated the blood alcohol level significantly at both 15 and 45 minutes after alcohol administration, but there was no significant difference in the blood alcohol level between the two subgroups in which nortriptyline was administered for 5 and 10 days respectively.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/115538
Appears in Collections:
2. 학위논문 > 1. College of Medicine (의과대학) > 석사
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