Fluphenazine, Lithium 및 L-dopa가 가토 혈중 주정농도에 미치는 영향에 관한 실험적 연구

Abstract

[한글]

Effects of fluphenazine, lithium and L-dopa on blood alcohol level in rabbits

Moon Hee Ju

Department of Medical Science, The Graduate School, Yonsei University

(Directed by Professor, Chae Won Kim, M.D.)

Lithium has lately been regarded as an extremely promising psychotropic drug in

treatment of mania, various other psychotic excitements and recurrence of both

manic and depressive symptoms. Fouphenazine, which is a potent and long acting

phenothiazine derivatives, has been used in treatment of the ambulatory and chronic

schizophrenic patients who need prolonged and continuous psychotropic medication.

It has been known that L-dopa is of particular value in controlling Parkinsonism by

increasing of the concentration of dopamine in basal ganglia.

In 1960, Khouw et al, reported that chlorpromazine elevated the blood alcohol

level in horse by the inhibition of alcohol dehydrogenase(ADH) in liver. Other

investigators have also been lately reported that lithium, some anti-depressants

and several psychotropic drugs elevated the blood alcohol level in rabbits. In view

of these findings, the author conducted an animal experiment to investigate the

effects of fluphenazine alone, in combination with lithium, and L-dopa alone on

blood alcohol level in rabbits.

Materials and Methods

1. The experimental work was done with mature rabbits of both sexes, weighing

between 2.0kg to 3.0kg.

2. The experimental animals were divided into two groups ; control and

experimental group. Control group was given alcohol alone, and experimental group

was further divided into four group; alcohol _ fluphenazine group, alcohol +

lithium group, alcohol + L-dopa group and alcohol + fluphenazine + lithium group.

3. Fluphenazine was given orally. Alcohol + fluphenazine group was divided into

two subgroups. In the first subgroup fluphenazine was given 10.mg/kg of body

weight, daily for 5 days, and in the second subgroup, 2.0mg/Kg body weight, daily

ofr 5 days. The last dose of fluphenazine was given 90 minutes before alcohol

administration.

4. L-dopa was given orally, in a dose of 50 mg/Kg of body weight, daily for 5

days. The last dose of L-dopa was given 90 minutes before alcohol administration.

5. Lithium chloride solution, 6.36%, was given, in a dose of 3.0 mEq/Kg of body

weight, daily for 4 days by intravenous route. The last dose was given 60 minutes

before alcohol administration.

6. In all groups, 20 vol.% ethanol solution was given, in a dose of 5.0 ml/Kg of

body weight, at a constant rate for 5 minutes, by intravenous route.

7. All of the blood specimens were obtained by cardiac puncture at 15 and 45

minutes respectively after alcohol administration.

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

Results

1. Alcohol + fluphenazine group

In the first subgroup, fluphenazine elevated the blood alcohol level at both 15

and 45 minutes after alcohol administration. But, at 15 minutes, the result was not

statistically significant(P>0.05).

In the second subgroup, fluphenazine elevated the blood alcohol level

significantly at both 15 and 45 minutes after alcohol administration(P<0.01).

2. Alcohol + lithium group

Lithium elevated the blood alcohol level significantly at both 15(P<0.01) and 45

minutes({<0.02) after alcohol administration.

3. Alcohol + L-dopa group

L-dopa lowered the blood alcohol level at both 15 and 45 minutes after alcohol

administration. However, the result at 15 minutes was not statistically

significant(P>0.05).

4. alcohol + fluphenazine + Lithium group

Fluphenazine combined with lithium elevated significantly the blood alcohol level

at both 15 and 45 minutes after alcohol administration(P<0.01). The blood alcohol

levels of this group were significantly higher than those of all subgroups of

alcohol + fluphenazine and alcohol + lithium group.

Conclusions

1. The orally administered fluphenazine, in a dose of 1.0 mg/Kg/day, for 5 days

and, in a dose of 2.0 mg/Kg/day, for 5 days elevated the blood alcohol level in

rabbits at both 15 and 45 minutes after alcohol administration.

But, at 15 minutes after administration of 1.0 mg/Kg/day for 5 days, the result

was not significant.

2. Intravenous injection of lithium chloride, in a dose of 3.0 mEq/Kg/day, for 4

days elevated significantly the blood alcohol level in rabbits at both 15 and 45

minutes after alcohol administration.

3. The orally administered L-dopa, in a dose of 500 mg/Kg/day, for 5 days lowered

significantly the blood alcohol level in rabbits at 45 minutes, but not at 15

minutes after alcohol administration.

4. The fluphenazine combined with lithium chloride elevated significantly the

blood alcohol level in rabbits at both 15 and 45 minutes after alcohol

administration.

[영문]

Lithium has lately been regarded as an extremely promising psychotropic drug in treatment of mania, various other psychotic excitements and recurrence of both manic and depressive symptoms. Fouphenazine, which is a potent and long acting phenothiazine derivatives, has been used in treatment of the ambulatory and chronic schizophrenic patients who need prolonged and continuous psychotropic medication.

It has been known that L-dopa is of particular value in controlling Parkinsonism by increasing of the concentration of dopamine in basal ganglia.

In 1960, Khouw et al, reported that chlorpromazine elevated the blood alcohol level in horse by the inhibition of alcohol dehydrogenase(ADH) in liver. Other investigators have also been lately reported that lithium, some anti-depressants and several psychotropic drugs elevated the blood alcohol level in rabbits. In view of these findings, the author conducted an animal experiment to investigate the effects of fluphenazine alone, in combination with lithium, and L-dopa alone on blood alcohol level in rabbits.

Materials and Methods

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

2. The experimental animals were divided into two groups ; control and experimental group. Control group was given alcohol alone, and experimental group was further divided into four group; alcohol _ fluphenazine group, alcohol + lithium group, alcohol + L-dopa group and alcohol + fluphenazine + lithium group.

3. Fluphenazine was given orally. Alcohol + fluphenazine group was divided into two subgroups. In the first subgroup fluphenazine was given 10.mg/kg of body weight, daily for 5 days, and in the second subgroup, 2.0mg/Kg body weight, daily

ofr 5 days. The last dose of fluphenazine was given 90 minutes before alcohol administration.

4. L-dopa was given orally, in a dose of 50 mg/Kg of body weight, daily for 5 days. The last dose of L-dopa was given 90 minutes before alcohol administration.

5. Lithium chloride solution, 6.36%, was given, in a dose of 3.0 mEq/Kg of body weight, daily for 4 days by intravenous route. The last dose was given 60 minutes before alcohol administration.

6. In all groups, 20 vol.% ethanol solution was given, in a dose of 5.0 ml/Kg of body weight, at a constant rate for 5 minutes, by intravenous route.

7. All of the blood specimens were obtained by cardiac puncture at 15 and 45 minutes respectively after alcohol administration.

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

Results

1. Alcohol + fluphenazine group

In the first subgroup, fluphenazine elevated the blood alcohol level at both 15 and 45 minutes after alcohol administration. But, at 15 minutes, the result was not statistically significant(P>0.05).

In the second subgroup, fluphenazine elevated the blood alcohol level significantly at both 15 and 45 minutes after alcohol administration(P<0.01).

2. Alcohol + lithium group

Lithium elevated the blood alcohol level significantly at both 15(P<0.01) and 45 minutes({<0.02) after alcohol administration.

3. Alcohol + L-dopa group

L-dopa lowered the blood alcohol level at both 15 and 45 minutes after alcohol administration. However, the result at 15 minutes was not statistically significant(P>0.05).

4. alcohol + fluphenazine + Lithium group

Fluphenazine combined with lithium elevated significantly the blood alcohol level at both 15 and 45 minutes after alcohol administration(P<0.01). The blood alcohol levels of this group were significantly higher than those of all subgroups of

alcohol + fluphenazine and alcohol + lithium group.

Conclusions

1. The orally administered fluphenazine, in a dose of 1.0 mg/Kg/day, for 5 days and, in a dose of 2.0 mg/Kg/day, for 5 days elevated the blood alcohol level in rabbits at both 15 and 45 minutes after alcohol administration.

But, at 15 minutes after administration of 1.0 mg/Kg/day for 5 days, the result was not significant.

2. Intravenous injection of lithium chloride, in a dose of 3.0 mEq/Kg/day, for 4 days elevated significantly the blood alcohol level in rabbits at both 15 and 45 minutes after alcohol administration.

3. The orally administered L-dopa, in a dose of 500 mg/Kg/day, for 5 days lowered significantly the blood alcohol level in rabbits at 45 minutes, but not at 15 minutes after alcohol administration.

4. The fluphenazine combined with lithium chloride elevated significantly the blood alcohol level in rabbits at both 15 and 45 minutes after alcohol administration.