Desipramine이 가토 혈중 주정농도에 미치는 영향에 관한 실험적 연구

Abstract

[한글]

Desipramine은 항우울제로써 tricyclic antidepressant의 대표적인 약물인 imipramine의 monomethyl 유도체이다.

이 약물은 내인성 우울에 특히 유효함이 다수의 연구결과로 밝혀졌으며, 다른 tricyclic antidepressant 약물보다 비교적 신속한 약리작용을 장접으로 하고 있다.

한편 일부 향정신성 약물 복용시 주정섭취로 인한 교통사고 유발 위험성이 증가되며, 또한 주정 중독환자들에게서는 우울이 그 역동적 주축(主軸)을 이루고 있는 바, 급만성 주정 중독의 치료시에 어떤 항우울제를 사용하는가 하는 문제가 있다. 특히 최근 다수의 항우울제가 가토 혈중 주정농도에 영향을 미친다는 일련의 실험결과에 비추어 강력한 항우울제 중 하나인 desipramine이 주정농도에 미치는 영향에 관한 연구는 이론적으로나 실제적으로 흥미있는 바로 고려되어 가토를 사용해 실험적으로 본 연구를 시행하였다.

실험재료 및 실험방법

1. 실험동물은 2.0 kg 내외의 성숙 자웅 가토를 사용하였다.

2. 비교군에서는 주정만 단독 투여하였다.

3. 실험군은 다음과 같이 4아군으로 구분하였다.

1) 주정 ＋ Desipramine 25 mg/kg 연 5일 투여군

2) 주정 ＋ Desipramine 25 mg/kg 연 10일 투여군

3) 주정 ＋ Desipramine 50 mg/kg 연 5일 투여군

4) 주정 ＋ Desipramine 50 mg/kg 연 10일 투여군

4. 주정 투여는 20% ethanol 용액을 체중 매 kg당 5.9㎖을 이변정맥(耳 靜脈) 내로 5분간에 걸쳐 서서히 정맥 주사하였다.

5. 채혈은 주정 투여후 15분과 45분에 심장 천자로 시행하였다.

6. 주정의 혈중 농도는 Cavett씨 방법에 의해 측정하였다.

실험결과

1. Desipramine을 25mg/kg씩 연 5일 및 연10일 투여시 주정 투여후 15분 및 45분 각각에서 모두 혈중 주정농도에 유의한 변화가 없었다.

2. Desipramine을 50mg/kg씩 연 5일 투여시 주정 투여후 15분에서는 혈중 주정농도를 유의하게 높였으나, 주정 투여후 45분에서는 유의한 변화가 없었다. 연 10일간 투여시 주정 투여후 15분 및 45분 모두에서 혈중 주정농도를 유의하게 높였다.

[영문]

Desipramine is the monomethyl analogue of imipramine and is introduced as a potent antidepressant agent of rapid action. Most recent reports of desipramine on depressed patients indicate an effectiveness similar to imipramine.

Investigators suggested that any new phschotropic drugs should be tested for its interaction with alcohol, because they might precipitate the risk situation in case of consuming them concurrently.

In view of these reports, the author conducted an animal experiment to investigate the effects of desipramine on blood alcohol level rabbits.

Material and Method

1. The experimental work was done on mature rabbits of both sexes, weighing about 2 kg.

2. The experimenta lanimals were divided into two groups, the control and the experimental group.

3. The control group was given alcohol alone.

4. The experimenta group was divided into 4 subgroups,

a) alcohol plus desipramine, 25 mg/kg of body weight for 5 days

b) alcohol plus desipramine, 25 mg/kg of body weight for 10 days

c) alcohol plus desipramine, 50 mg/kg of body weight for 5 days

d) alcohol plus desipramine, 50 mg/kg of body weight for 10 days

5. Desipramine was given orally in a single dose at a fixed time. The last dose was given one hour and a half before alcohol administration.

6. In all groups 20% ethanol solution was slowly given in a dose of 5.0 mg/kg of body weight for 5 minutes by intravenous route.

7. All of the blood specimens were obtained by cardiac puncture at both 15 and 45 minutes after alcohol administration.

8. The determination of blood alcohol level was made by Cavett's method.

Results

1. Alcohol plus desipramine, 25 mg/kg of body weight for 5 days. Desipramine did not change the blood alcohol level significantly at both 15 and 45 minutes after alcohol administration (p>0m05).

2. Alcohol plus desipramine, 25 mg/kg of body weight for 10 days. In this group, these was also no significant change in the blood level at both 14 and 45 minutes after alcohol administration (p>0,05)

3. Alcohol plus desipramine, 50 mg/kg of body weight for 5 days. In this group, desipramine elevated the blood alcohol level significantly at 15 minutes after alcohol administration (p<0.02), while there was no significant change in the blood alcohol level at 45 minutes after alcohol administration (p>0.05).

4. Alcohol plus desipramine, 50 mg/kg of body weight for 10 days. In this group, desipramine elevated the blood alcohol level significantly at both 15 (p<0.001) and 45 (p<0.002) minutes after alcohol administration.

Comparing these results of desipramine, the length of duration administering this drug and its dosage seemed to attribute to the elevation of the blood level of alcohol in rabbits.

Conclusion

1. Desipramine when administered orally in a dose of 25 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, Desipramine when administered orally in a dose of 50 mg/kg of body weight daily for 5 days, elevated the blood alcohol level significantly at 15 minutes after alcohol administration, while there was no significant change in the blood alcohol level at 45 minutes after alcohol administration. But, desipramine when

administered orally in the same dose daily for 10 days, elevated the blood alcohol level significantly at both 15 and 45 minutes after alcohol administration.