Dibenzepine이 가토 혈중 주정 농도에 미치는 영향에 관한 실험적 연구

Abstract

[한글]

Dibenzepine은 새로운 tricyclic antidepressant이며 dibenzodiazepine의 유도체이다.

이 약물은 항불안작용을 수반해 내인성 우울뿐아니라 퇴행성 우울, 반응성 우울등 전반적인 우울상태에 효과적임이 다수의 임상 결과에서 보고됐으며 다른 tricyclic antidepressant에 비해 신속한 약리작용에도 불구하고 경미한 부작용을 일으키므로 안전한 약물로 인정되고 있다.

한편 일부 향정신성 약물 복용시 주정섭취로 인한 교통사고 유발 위험성이 증가되며 최근 다수의 항우울제가 가토 혈중 주정농도에 영향을 미친다는 일련의 실험결과에 비추어 강력한 항우울제의 하나인 dibenzepine이 주정농도에 미치는 영향에 관한 연구는 이론적으로나 실제적으로 흥미있는 바로 고려되어 가토를 사용해 실험적으로 본 연구를 시행하였다.

실험재료 및 실험방법

1. 실험동물은 체중 2.0 kg 내외의 성숙 자웅 가토를 사용하였다.

2. 비교군에서는 주정만 단독 투여하였다.

3. 실험군은 다음과 같이 4아군으로 나누었다.

a) 주정 + dibenzepine 1일 80 mg/kg 연 5일 투여군

b) 주정 + dibenzepine 1일 80 mg/kg 연 10일 투여군

c) 주정 + dibenzepine 1일 160 mg/kg 연 5일 투여군

d) 주정 + dibenzepine 1일 160 mg/kg 연 10일 투여군

4. 주정 투여는 20% ethanol용액을 체중 매 kg당 5.0 ml를 이변정맥내로 5분간에 걸쳐 서서히 정맥 주사하였다.

5. 채혈은 주정 투여후 15분간 45분에 심장 천자로 시행하였다.

6. 주정의 혈중 농도는 Cavett씨 방법에 의해 측정하였다.

실험결과

1. Dibenzepine을 1일 80 mg/kg씩 각기 연 5일 및 연 10일간 투여시 주정 투여후 15분 및 45분 각각에서 모두 혈중 주정농도에 유의한 변화가 없었다.

2. Dibenzepine을 1일 160 mg/kg씩 각기 연 5일 투여시 주정 투여후 15분 및 45분 각각에서 모두 혈중 주정농도에 유의한 변화가 없었다. 연 10일간 투여시 주정 투여후 15분 및 45분 모두에서 혈중 주정농도를 유의하게 높였다.

[영문]

Dibenzepine is a new dibenzeodizepine derivative with tricyclic chemical configuration. Chemically, it is 10-[2-(dimethylamino)ethy]-5, 10-dihydro-5-methyl-11-H-dibenzo[b,e][1,4] diazepine-11-one Hydrochloride.

In the clinical investigation, it was found to have moderate anxiolyic and thymoanaleptic action and to be safe drug. It has mild or transient side effect and good tolerance, even in larger dosage. It shows more rapid drug response, and is suitable to use in outpatient treatment.

Many clinicial investigators have suggested that dibenzepine is indicated for depression of endogenous, endoreactive and reactive origin, involutional and organic depression.

Also, investigators suggested that any new psychotropic 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 dibenzepine on blood alcohol level in rabbits.

Material and Method

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

2. The experimental animals were divided into two groups: the control and the experimental group.

3. The control group was given alcohol alone.

4. The experimental group was divided into 4 subgroups:

a) alcohol plus dibenzepine, 80mg/kg of body weight daily for 5 days.

b) alcohol plus dibenzepine, 80mg/kg of body weight daily for 10 days.

c) alcohol plus dibenzepine, 160mg/kg of body weight daily for 5 days.

d) alcohol plus dibenzepine, 160mg/kg of body weight daily for 10 days.

5. Dibenzepine 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 5.0ml/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 dibenzepine, 80mg/kg of body weight daily for 5 days. Dibenzepine did not change the blood alcohol level significantly at both 15 and 45 minutes after alcohol administration (p>0.05).

2. Alcohol plus dibenzepine, 80mg/kg of body weight daily for 10 days. In this group, these was also no significant change in the blood level at both 15 and 45 minutes after alcohol administration (p>0.05)

3. Alcohol plus dibenzepine, 160mg/kg of body weight daily for 5 days. In this group, these was also no significant change in the blood level at both 15 and 45 minutes after alcohol administration (p>0.05).

4. Alcohol plus dibenzepine, 160mg/kg of body weight daily for 10 days. In this group, dibenzepine elevated the blood alcohol level significantly at both 15 (p<0.02) and 45 (p<0.02) minutes after alcohol administration.

Conclusion

1. Dibenzepine when administered orally in a dose of 80mg/kg of body weight dialy for 5 or 10 days, did not change the blood alcohol level significantly at both 15 and 45 minutes after alcohol administration.

2. Dibenzepine, when administered orally in a dose of 160mg/kg of body weight dialy for 5 days, did not elevate the blood slcohol level significantly at both 15 and 45 minutes after alcohol administration.

But dibenzepine, 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.