Sodium bromide 및 temazepam이 가토혈중 alcohol 농도에 미치는 영향에 관한 실험적 연구

Abstract

[한글]

Temazepam은 1,4-benzodiazepine계 항불안제로서 현재 임상에 널리 사용되고 있다. Sodium bromide는 1940년대까지 항경련제 및 안정제로서 널리 사용되었었으며, 현재에도 간혹 대발작과 초점성 간질에 사용되고 있다.

향정신성 약물을 복용하는 환자들에게서 음주로 인한 사고의 위험이 증가하고 있기 때문에 주정과의 상호 작용을 알아보는 것이 중요하며 급만성 주정 중독환자의 치료에 어떤 약물을 선택할 것인가 하는 점은 중요한 관심사가 되어 왔다. 이러한 사실에서 Temazepam 및 Sodium bromide가 가토 혈중 주정 농도에 미치는 영향을 규명해 봄은 이론적으로나실제적으로 의의있는 바로 고려되어 본 연구를 시행하였다.

실험 재료 및 실험 방법

1. 실험 동물은 체중 2.0 kg 내외의 성숙 자웅 가토를 사용하였다.

2. 비교군에서는 주정만 단독 투여하였다.

3. 실험군은 다음과 같이 6아군으로 구분하였다.

1) 주정+ Sodium bromide 1일 0.5g/kg 연3일 투여군

2) 주정+ Sodium bromide 1일 0.5g/kg 연7일 투여군

3) 주정+ Sodium bromide 1일 0.5g/kg 연10일 투여군

4) 주정+ Temazepam 1일 10mg/kg 연3일 투여군

5) 주정+ Temazepam 1일 10mg/kg 연7일 투여군

6) 주정+ Temazepam 1일 10mg/kg 연10일 투여군

4. 주정 투여는 20% ethanol용액을 체중 매 kg당 0.5㎖를 이변정맥내로 5분간에 걸쳐서서히 주사하였다.

5. 채혈은 주정 투여후 15분과 45분에 심장 천자로 시행하였다.

6. 주정의 혈중 농도는 Cavett씨 방법에 의해 측정하였다.

실험결과

1. Sodium bromide를 1일 0.5g/kg씩 연3일 투여시 주정투여후 15분 및 45분에서 각기혈중 주정 농도에 유의한 변화가 없었다. 연7일 및 연10일간 투여시 주정 투여후 15분 및 45분 모두에서 혈중 주정 농도가 유의하게 높았다.

2. Temazepam을 1일 10mg/kg씩 연3일 투여시 주정 투여후 15분 및 45분에서 각기 혈중주정 농도에 유의한 변화가 없었다. 연7일 및 연10일간 투여시 주정 투여후 15분 및 45분 모두에서 혈중 주정 농도가 유의하게 높았다.

[영문]

Temazepam is one of 1,4-benzodiazepine derivatives widely used as a hypnotic and anxiolytic in clintcal medicine. Chemically, it is 7-chloro-1,3-dehydro-3-hydroxy-1-methyl-5-phenyl-2H-1,4- benzodiazepine-2-one. The sedative, anti-convulsant, and antianxiety effects of temazepam on experimental animals resemble those of other benzodiazepines. It is also proved to be effective

as a safe and potent hypnotic.

Sodium bromide was widely used as anticonvulsant and sedative until 1940s. It is still used occasionally in the treatment of grand mal and focal epilepsy. In some respects, sodium bromide was taking the place where temazepam now occupies. The author conducted an animal experiment to investigate the effect of temazepam and sodium bromide on blood alcohol level, because many investigators have suggested that many psychotropic drugs elevated 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) Sodium bromide 0.5g/kg/day for 3days plus alcohol

b) Sodium bromide 0.5g/kg/day for 7days plus alcohol

c) Sodium bromide 0.5g/kg/day for 10days plus alcohol

d) Temazepam 10mg/kg/day for 3days plus alcohol

e) Temazepam 10mg/kg/day for 7days plus alcohol

f) Temazepam 10mg/kg/day for 10days plus alcohol

5. Temazepam and sodium bromide were given orally in a single dose daily at a fixed time, respectively. 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 5.0mg/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. Sodium bromide 0.5g/kg/day for 3days plus alcohol Sodium bromide did not change the blood alcohol level significantly at both 15 and 45 minutes after alcohol administration. (respectively, p>0.05, p>0.4)

2. Sodium bromide 0.5g/kg/day for 7days plus alcohol Sodium bromide elevated the blood alcohol level significantly at both 15 and 45 minutes after alcohol administration. (respectively, p<0.001)

3. Sodium bromide 0.5g/kg/day for 10days plus alcohol Sodium bromide elevated the blood alcohol level significantly at both 15 and 45 minutes after alcohol administration. (respectively, p<0.001)

4. Temazepam 10mg/kg/day for 3days plus alcohol Temazepam did not change the blood alcohol level significantly at both 15 and 45 minutes after alcohol administration. (respectively, p>0.2, p>0.1)

5. Temazepam 10mg/kg/day for 7days plus alcohol Temazepam elevated the blood alcohol level significantly at both 15 and 45 minutes after alcohol administration. (respectively, p<0.01, p<0.001)

6. Temazepam 10mg/kg/day for 10days plus alcohol Temazepam elevated the blood alcohol level significantly at both 15 and 45 minutes after alcohol administration. (respectively, p<0.001)

Conclusion

1. Sodium bromide, when administered orally in a dose of 0.5g/kg of body weight for 3days did not change the blood alcohol level significantly at both 15 and 45 minutes after alcohol administration. But sodium bromide, when administered orally

in the same dose daily for 7 and 10 days elevated the blood alcohol level significantly at both 15 and 45 minutes after alcohol administration.

2. Temazepam, when administered orally in a dose of 10mg/kg of body weight for 3 days did not change the blood alcohol level significantly at both 15 and 45 minutes after alcohol administration. But, temazepam, when administered orally in the same dose daily for 7 and 10 days elevated the blood alcohol level significantly at both 15 and 45 minutes after alcohol administration.