Clobazam이 가토 혈중 주정 농도에 미치는 영향에 관한 실험적 연구

Abstract

[한글]

Clobazam은 최근에 개발된 첫 1.5-benzodiazepine유도체로써 1.4-benzodiazepine 유도체들과 유사한 성상이 있는 항불안제로 임상에 사용되고 있다.

이 약물은 임상적으로 taming effect, 항경련 작용, 항불안 작용 및 긴장완화 작용 등이 밝혀져 각종의 신경증 및 정신 신체 질환에 사용되고 있다.

한편, 항불안제의 복용시 주정 섭취로 인한 사고유발 위험성이 증가하고 있기 때문에 주정과의 상호작용을 규명해 봄은 이론적으로나 실제적으로 의의있는 것으로 사료되어 본 연구를 시행하였다.

실험재료 및 실험방법

1. 실험동물은 2∼3kg의 성숙한 가토를 사용하였다.

2. 비교군에서는 주정만 단독 투여하였다.

3. 실험군은 다음과 같이 6아군으로 구분하였다.

1) 주정+clobazam 20mg/kg/day 연 5일 투여군

2) 주정+clobazam 20mg/kg/day 연 10일 투여군

3) 주정+clobazam 30mg/kg/day 연 5일 투여군

4) 주정+clobazam 30mg/kg/day 연 10일 투여군

5) 주정+clobazam 40mg/kg/day 연 5일 투여군

6) 주정+clobazam 40mg/kg/day 연 10일 투여군

4. 주정 투여는 20% ethanol용액을 체중 kg당 5.0 ml를 이변 정맥내로 5분간에 걸쳐 서서히 주사하였다.

5. 채혈은 주정 투여후 15분과 45분에 삼장 천자로 시행하였다.

6. 주정의 혈중 농도는 Cavett씨 법에 의해 측정하였다.

실험결과

1. Clobazam을 20mg/kg/day로 연 5일 및 연 10일 투여시 주정 투여후 15분 및 45분에서 각기 혈중 주정 농도에 유의한 변화가 없었다.

2. Clobazam을 30mg/kg/day로 연 5일 및 연 10일 투여시 주정 투여후 15분 및 45분에서 각기 혈중 주정 농도에 유의한 변화가 없었다.

3. Clobazam을 40mg/kg/day로 연 5일 및 연 10일 투여시 주정 투여후 15분 및 45분에서 각기 혈중 주정 농도에 유의한 변화가 없었다.

[영문]

Clobazam is an anxiolytic drug which belongs to the class of the 1,5-rather than the 1,4-benzodiazepines. The structural difference between clobazam and other benzodiazepines is that the nitrogen in the heterocyclic ring is in positions 1 and 5 rather than in position 1 and 4.

This drug possesses all the pharmacological properties of a anti-anxiety agent without appreciable sedative and depressives side-effects.

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.

Recently it has been reported that various psychotropic agents tended to elevate the blood alcohol level.

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

Material and Method

1. The experimental work was done on mature rabbits of both sexes, weighing about 2.0Kg.

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 6 subgroups:

a) alcohol plus colbazam, 20mg/kg of body weight daily for 5 days.

b) alcohol plus clobazam, 20mg/kg of body weight daily for 10 days.

c) alcohol plus clobazam, 30mg/kg of body weight daily for 5 days.

d) alcohol plus clobazam, 30mg/kg of body weight daily for 10 days.

e) alcohol plus clobazam, 40mg/kg of body weight daily for 5 days.

f) alcohol plus clobazam, 40mg/kg of body weight daily for 10 days.

5. Clobaxam was given orally in a single daily dose at the 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 respectively, after alcohol administration.

8. The blood alcohol level was determined by Cavett's Method.

Results

1. Alcohol plus clobazam, 20mg/kg of body weight daily for 5 days. Clobazam did not change the blood alcohol level significantly at both 15 and 45 minutes after alcohol administration. (respectively. P>0.05).

2. Alcohol plus clobazam, 20mg/kg body weight daily for 10 days. In this group, there was no significant change in the blood level at both 15 and 45 minutes after alcohol administration (respectively, P>0.05).

3. Alcohol plus clobazam, 30mg/kg of body weight daily for 5 days. In this group, there was no sigificant change in the blood level at both 15 and 45 minutes after alcohol administration (respectively, P>0.05).

4. Alcohol plus clobazam, 30mg/kg of body weight daily for 10 days. In this group, there was no significant change in the blood level at both 15 and 45 minutes after alcohol administration (respectively, P>0.05).

5. Alcohol plus clobazam, 40mg/kg of body weight daily for 5 days. In this group, there was no significant change in the blood level at both 15 and 45 minutes after alcohol administration (respectively, P>0.05).

6. Alcohol plus clobazam, 40mg/kg of body weight daily for 10 days. In this group, there was no significant change in the blood at both 15 and 45 minutes after alcohol administration(respectively, P>0.05).

Conclusion

1. Clobazam, when administered orally in a dose of 20mg/kg body weight daily for 5 or 10 days, did not change the blood alcohol level significantly at both 15 and 45 minutes after alcohol administration.

2. Clobazam, when administered orally in a dose of 30mg/kg of body weight daily for 5 or 10 days, did not change the blood alcohol level significantly at both 15 and 45 minutes after alcohol administration.

3. Clobazam, when administered orally in a dose of 40mg/kg of body weight daily for 5 or 10 days, did not change the blood alcohol level significantly at both 15 and 45 minutes after administration.