Imipramine 및 Lithium이 가토혈중 주정 농도에 미치는 영향에 관한 실험적 연구

Abstract

[한글]

[영문]

Imipramine, a tricyclic antidepressant, was synthesized by Hafliger in 1948.

Kuhn, in 1958, found imipramine was remarkably effective in certain depressed

states, especially in endogenous depression. since then, further evidences for the

effectiveness of this compound have been accumulated.

Lithium, a monovalent cation and the lightest alkali metal, was discovered in

1818 by Arfwedson. Since Cade, in 1949, found that lithium carbonate caused

sedation in guinea pigs and that it did calm manic patients, numerous studies have

indicated that the drug is effective in the control of mania and other psychotic

excitement and also in prevention of manic depressive episodes.

It has lately been reported that lithium and several other psychotropic drugs

elevated the blood alcohol level in rabbits. In views of these reports the author

conducted an animal experiment to investigate the effects of imipramine and

lithium, alone or in combination, on blood alcohol level in rabbits.

Materials and Methods

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

between 2.0 Kg and 3.0 Kg.

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

experimental group.

3. The control group was given alcohol alone.

4. The experimental group was divided into 5 groups; Ⅰ) alcohol + lithium, Ⅱ)

alcohol + imipramine (I.M.), Ⅲ) alcohol + lithium + imipramine (I.M.), Ⅳ) alcohol

+ imipramine(oral), and Ⅴ) alcohol + lithium + imipramine(oral) group.

5. Alcohol + imipramine(I.M.) group was further divided into 4 subgroups,

according to the time of alcohol injection; alcohol administration immediately, 10,

20, and 30 minutes after imipramine injection.

6. Alcohol + imipramine(oral) group and alcohol + lithium + imipramine(oral)

group were further divided into 2 subgroups in which one subgroup was given

imipramine for 7 days and another for 14 days.

7. 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 1 hour before

alcohol administration.

8. Imipramine was given intramuscularly in a single dose of 2.0 mg/Kg of body

weight. In case of oral administration imipramine was given in a dose of 4.0 mg/Kg

of body weight daily for 7 days or for 14 days. The last dose was given one hour

before alcohol administration.

9. In all groups 20% ethanol solution was given in a dose of 5.0 ml/Kg of body

weight in 5 minutes by intravenous route.

10. All of the blood specimens were obtained by cardiac puncture at 10 and 30

minutes after alcohol administration.

11. The blood alcohol level determination was made by Cavett's method.

Results

1. Alcohol + lithium group

Lithium elevated the blood alcohol level significantly both at 10 and 30 minutes

after alcohol administration (P〈0.05).

2. Alcohol + imipramine (I.M.) group

Imipramine elevated the blood alcohol level significantly both at 10 and 30

minutes after alcohol administration in the first subgroup in which alcohol was

given immediately following imipramine injection (P〈0.05).

In the second and third subgroup, the blood alcohol level was elevated

significantly only at 10 minutes, but not at 30 minutes after alcohol

administration. There was no significant change in the blood alcohol level in the

fourth subgroup.

3. Alcohol + lithium + imipramine (I.M.) group

Imipramine combined with lithium elevated the blood alcohol level significantly

both at 10 and 30 minutes after alcohol administration (P〈0.05).

4. Alcohol + imipramine(oral) group

Imipramine elevated the blood alcohol level significantly at 10 and 30 minutes

after alcohol administration in the subgroups in which imipramine was administered

either for 7 or 14 days (P〈0.05).

But there was no significant difference in the blood alcohol level between these

two subgroups (P〉0.05).

5. Alcohol + lithium + imipramine(oral) group

Imipramine(oral) combined with lithium elevated the blood alcohol level

significantly at 10 and 30 minutes after alcohol administration in both subgroups

in which imipramine was administered either for 7 or 14 days (P〈0.05). The blood

alcohol level of these two subgroups was significantly higher than either that of

lithium alone group or imipramine(oral) alone group (P〈0.05).

6. Above experimental results were analysed statistically between the control

group and each experimental group, and also among the experimental group.

Conclusion

1. The intravenous injection of 6.36% lithium chloride solution in a dose of 3.0

mEq/Kg of body weight daily for 4 days elevated the blood alcohol level in rabbits

significantly both at 10 and 30 minutes after alcohol administration.

2. Imipramine administered intramuscularly in a single dose of 2.0 mg/kg of body

weight showed variable effects on the blood alcohol level according to the time of

alcohol administration after imipramine injection. The blood alcohol level was

elevated both at 10 and 30 minutes after alcohol administration in the subgroup in

which alcohol was administered immediately after imipramine injection. And in the

subgroups in which alcohol was administered at 10 and 20 minutes after imipramine

injection, the blood alcohol level was elevated only at 10 minutes after alcohol

administration.

3. Imipramine administered orally in a dose of 4.0 mg/kg of body weight daily for

7 or 14 days elevated the blood alcohol level significantly both at 10 and 30

minutes after alcohol administration. There was no significant difference in the

blood alcohol level between the two subgroups in which imipramine was administered

for 7 or 14 days.

4. Imipramine when combined with lithium elevated the blood alcohol level

significantly at 10 and 30 minutes after alcohol administration in both orally and

intramuscularly administered groups. In the former group the blood alcohol level

was significantly higher than that of imipramine alone or lithium alone group.