Mesoridazine이 가토 혈중 주정농도에 미치는 영향에 관한 실험적 연구

Abstract

[한글]

Mesoridasine은 phenothiazine 중 piperidine 유도체중의 하나인 thioridasine의 한 대사간물이다. 이 약물은 thioridazine 및 chlorpromazine과 비슷한 점이 많은 정온제로서 중추신경계에 대한 억제작용 및 진정작용을 갖고 있고, 부작용은 다른 phenothiazine계

약물들에 비해 경미하고 특성이 낮아 안전한 약물로 인정되고 있다.

한편 정온제의 복용시 주정 섭취로 인한 사고 유발 위험성이 증가하고 있기 때문에 주정과의 상호작용을 알아보는 것이 중요하다고 주장되고 있다. 최근 chlorpromazine과 lithium을 포함하는 많은 향정신성 약물들이 가토 혈중 주정농도를 높인 것으로 보고 되었다. 이런 사실에 비추어 mesoridazine이 가토 혈중 주정농도에 미치는 영향을 규명해 봄은 이론적으로나 실제적으로 의의있는 바로 고려되어 본 연구를 시행하였다.

실험재료 및 실험방법

1. 실험동물은 체중 2.0kg∼3.0kg의 성숙자웅 가토를 사용하였다.

2. 비교군에서는 주정만 단독 투여하였다.

3. 실험군은 다음과 같이 4아군으로 구분하였다.

1) 주정+mesoridazine 1일 10mg/kg 연 5일 투여군

2) 주정+mesoridazine 1일 10mg/kg 연 10일 투여군

3) 주정+mesoridazine 1일 20mg/kg 연 5일 투여군

4) 주정+mesoridazine 1일 20mg/kg 연 10일 투여군

4. 주정투여는 20% ethanol 용액을 제중 매 kg당 5.0ml을 이변정맥(耳 靜脈)내로 5분간에 걸쳐 서서히 정맥주사하였다.

5. 채혈은 주정투여후 15분과 45분에 심장천자로 시행하였다.

6. 주정의 혈중농도는 Cavett씨 법에 의해 측정하였다.

실험결과

1. Mesoridazine을 1일 10mg/kg씩 연 5일 및 연 10일간 투여시, 주정투여후 15분 및 45분에서 각기 혈중 주정 농도에 유의한 변화가 없었다.

2. Mesoridazine을 1일 20mg/kg씩 연 5일 및 연 10일간 투여시, 주정투여후 15분 및 45분에서 각기 혈중 주정 농도를 유의하게 높였다.

[영문]

Mesoridazine, the side chain sulfoxide derivative of thioridazine, is a well-established and effective phenothiazine. Shemically, it is 10-[2(l-methyl-2-piperidyl)ethy1]-2(methyl-sulfinyl) phenothiazine. Mesoridazine possesses many of the pharmacologic properties of thioridazine and chlorpromazine,

and in the clinical investigation, it has attested to its efficacy and safety in psychiatric states such as schizophrenic patients, alcoholism, personality disorder, behavioral disorders in children and geriatric patients.

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.

It has been lately reported that chlorpromazine, lithium ion and several other psychotropic drugs elevated the blood alcohol level in expreimental animals.

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

Material and Method

1. The experimental work was done on mature rabbits of both sexes, weighing between 2.0kg and 3.0kg.

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

3. The Contol group was given alcohol alone.

4. The experimental group was divided into 4 subgroups:

a) alcohol plus mesoridazine, 10mg/kg of body weight daily for 5 days.

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

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

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

5. Mesoridazine 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 5.0ml/kg of body weight for 5 minutes by intravenous route.

7. All of the blood specimeus 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 mesoridazine, 10mg/kg of body weight dialy for 5 days.

Mesoridazine did not change the blood alcohol level significantly at both 15 and 45 minutes after alcohol administration (respectively, P>0.05).

2. Alcohol plus mesoridazine, 10mg/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).

3. Alcohol plus mesoridazine, 20mg/kg of body weight daily for 5 days.

In this group, mesoridazine elevated the blood alcohol level significantly at both 15 (P<0.01) and 45 (P<0.001) minutes after alcohol administration.

4. Alcohol plus mesoridazine, 20mg/kg of body weight daily for 10 days.

In this group, mesoridazine elevated the blood alcohol level significantly at both 15 (P<0.01) and 45 (P<0.02)minutes after alcohol administration.

Conclusion

1. Mesoridazine, when administered orally in a dose of 10mg/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.

2. Mesoridazine, when administered orally in a dose of 20mg/kg of body weight daily for 5 or 10 days, elevated the blood alcohol level significantly at both 15 and 45 minutes after alcohol administration.