Propranolol이 가토혈중 주정농도에 미치는 영향에 관한 실험적 연구

Abstract

[한글]

항불안제로서의 새로운 가능성에 대해 주목을 받고 있는 propranolol은 beta adrenergic receptor blocking agent의 하나로 입상에서 심장혈관계 질환의 치료에 사용되어 왔던 바 최근에는 정신분열증의 치료와 주정중독과 관련된 불안, 숙취 및 금단증상의 치료에도 효과가 있었다는 보고들이 있다. 그러나 propranolol의 이러한 효과가 중추 신경계에 대한 직접 작용 결과인지, 말초에서의 β-blocking effect에 의한 feed-back 효과의 결과인지 혹은 주정 대사작용에 관여한 결과인지는 명확히 알려져 있지 않다.

임상 실제에서 향정신성 약물을 복용하는 환자들은 그 역동학적 동기 때문에 음주의 가능성이 높고, 한편 주정중독 환자의 치료에 적절한 약물의 선택문제가 대두되고 있어, propranolol이 주정대사에 미치는 영향을 규명해 봄은 매우 의의 있는 일이라 생각되어 본 실험적 연구가 시행되었다.

실험 재료 및 방법

1. 실험동물은 성숙한 자웅 가토를 사용하였고 대조군은 주정만 단독 투여하였다.

2. 실험군은 약물 1일 용량에 따라 다음과 같이 4군으로 구분하였다.

① 주정+propranolol 10 mg/kg

② 주정+propranolol 20 mg/kg

③ 주정+propranolol 40 mg/kg

④ 주정+propranolol 60 mg/kg

3. 각 군은 연 5일간 및 10일간 투여한 두 아군으로 다시 구분하였다.

4. 주정 투여는 20 vol. % ethanol 용액을 체중 매 kg당 5ml씩 이변정맥내로 주사하였다.

5. 주정 투여후 15분과 45분에 심장천자로 채혈하였고 주정의 혈중농도 측정은 cavett씨 방법에 의하였다.

실험 결과

1. propranolol 1일 10 mg/kg을 연 5일 및 10일 투여시 주정 투혀후 15분 및 45분에서 혈중 주정 농도의 유의한 변화가 없었다.

2. propranolol 1일 20 mg/kg, 40 mg/kg을 연 5일 및 10일 투여시는 주정 투여후 각각 15분 및 45분에서 혈중 주정 농도가 대조군에 비해 유의하게 낮았다.

3. propranolol 1일 60 mg/kg을 연 5일 투여시 주정 투여후 45분에서, 그리고 같은 양을 연 10일 투여시 주정 투여후 15분과 45분에서 각각 주정의 혈중 농도는 대조군에 비해 유의하게 높았다.

[영문]

Propranolol, one of the beta adrenergic blocking agents, has been used for lthe treatment of cardiovascular disorders. Becently a few clinical investigators have reported that this drug can be used as an antianxiety agent. Several reports suggest that beta blockers may be of value in the treatment of alcohol withdrawl, anxiety associated with alcoholism and possibly as a hangover remedy. Some central mechanism of action has been suggested to explain the beneficial effect of propranolol. But other authors reported that propranolol may alleviate anxiety

through a peripheral mechanism, perhaps the feed-back loop.

It has been reported that many psychotropic druge including chlorpromazine, lithium and benzodiazepine derivatives potentiates the alcohol effects or blood alcohol level in experimental animals. In view of this findings, the author

conducted an animal experiment to investigate the effects of propranolol 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 two groups; the control and the experimental group. The control group was given alcohol alone.

3. The experimental group was divided into 4 subgroups;

a) alcohol plus propranolol, 10mg/kg of body weight daily.

b) alcohol plus propranolol, 20mg/kg of body weight daily.

c) alcohol plus propranolol, 40mg/kg of body weight daily.

d) alcohol plus propranolol, 60mg/kg of body weight daily.

4. These above groups were further divided into 2 subgroups: one subgroup was given the drug for 5 days and another for 10 days.

5. Propranolol was orally given in a single dose at a fixed time.

6. Alcohol was given two hours after the last dose of propranolol. 20vol.% 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 the blood alcohol level was made by Cavett's method.

Result

1. Alcohol plus propranolol, 10mg/Kg of body weight daily for 5 days. Propranolol caused no significant changes in blood alcohol level at both 15 and 45 minutes after alcohol administration. (P>0.5, P>0.1)

2. Alcohol plus propranolol, 10mg/Kg of body weight daily for 10 days. Propranolol caused no significant changes in blood alcohol level at both 15 and 45 minutes after alcohol administration. (P>0.1, P>0.1)

3 Alcohol plus propranolol, 20mg/Kg of body weight daily for 5 days. In this group, propranolol lowered the blood alcohol level significant at both 15 and 45 minutes after alcohol administration. (P<0.001, P<0.001)

4. Alcohol plus propranolol, 20mg/Kg of body weight daily for 10 days. In this group, propranolol lowered the blood alcohol level significantly at both 15 and 45 minutes after alcohol administration. (P<0.005, P<0.05)

5. Alcohol plus propranolol, 40mg/Kg of body weight daily for 5 days. In this group, propranolol lowered the blood alcohol level significantly at both 15 and 45 minutes after alcohol administration. (P<0.001, P<0.025)

6. Alcohol plus propranolol, 40mg/Kg of body weight daily for 10 days. In this group, propranolol lowered the blood alcohol level significantly at both 15 and 45 minutes after alcohol administration. (P<0.005, P<0.005)

7. Alcohol plus propranolol 60mg/Kg of body weight daily for 5 days. In this group, propranolol caused no significant change in the blood alcohol level at 15 minutes after alcohol administration, while at 45 minutes, propranolol elevated the

blood alcohol level significantly. (P>0.005, P<0.025)

8. Alcohol plus propranolol 60mg/Kg of body weight daily for 10 days. In this group, propranolol elevated blood alcohol level significantly at both 15 and 45 minutes after alcohol administration. (P<0.001, P<0.005)

Conclusion

1. Propranolol in a dose of 10mg/Kg of body weight daily for 5 or 10 days, caused no significant change in the blood alcohol level at both 15 and 45 minuted after alcohol administration.

2. Propranolol in a dose of 20mg/Kg, 40mg/Kg of body weight daily for 5 or 10 days, lowered the blood alcohol level significantly.

3. Propranolol in a dose of 60mg/Kg of body weight daily for 5 days caused no significant change in blood alcohol level at 15 minutes after alcohol administration, but elevated significantly at 45 minutes. Propranolol in a same dose daily for 10 days elevated the blood alcohol level significantly at both 15 and 45 minutes after alcohol administration.