In 1962, Sulser et al. first demonstrated that the antidepressant action of amitriptyline is mediated through a metabolic product, desmethylamitripty´ine (nortriptyline). And nortriptyline was synthesized by Dr. H. Spiegelberg and Dr. ,G. Rey-Bellet.
Thereafter numerous studies have indicated that nortriptyline is effective in the endogenous depre-:ssion. Since Hammer et al., in 1967, found that an apparent steady-state plasma level is achieved by repetitive oral administration of nortriptyline at fixed intervals, the enormous studies of the metabolism of nortriptyline have been done. Alexanderson et al., in 1969, performed the pharmacokinetic studies with nortriptyline in 78 twins, and it is found that nortriptyline kinetics in man is under the polygenic control.
Lawton and Cahn had suggested that any new psychotropic drugs should be tested for its interaction with alcohol, because they had been shown to increase the dangers of consuming´ alcoholic ,beverage.
Recently it has been reported that various psychotropic and antidepressant drugs elevated the blood alcohol level in rabbits. In view of these reports, the author conducted an animal experiment to investigate the effects of nortriptyline on 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 2 groups; the control and the experimental group.
3. The control group was given alcohol alone.
4. The- experimental group was divided into 2 subgroups; a) alcohol plus nortriptyline, 10mg/kg of body weight, and b) alcohol plus nortriptyline, 20mg/kg of body weight group.
5. Each alcohol plus nortriptyline group was further divided into 2 subgroups in which one subgroup was given nortriptyline for 5 days and another for 10 days.
6. Nortriptyline was orally given in a single dose at a fixed time. The last dose was given one hour and a half before alcohol administration.
7. In all groups 20% ethanol solution was slowly given in a dose of 5.Oml/kg of body weight in 5 minutes by intravenous route.
8. All of the blood specimens were obtained by cardiac puncture at 15 and 45 minutes after alcohol administration.
9. The blood alcohol level determination was made by Cavett´s method.
Results
1. Alcohol plus nortriptyline,,_ 10 mg/kg of body weight for 5 days. Nortriptyline did not change the blood alcohol level significantly at both 15 and 45 minutes after alcohol administration (P >0.4) .
2. Alcohol plus nortriptyline, 10 mg/kg of body weight for 10 days. In this group, there was also no significant change in the blood alcohol administration (P>0.4).
3. Alcohol plus nortriptyline, 20 mg/kg of body weight for 5 days. In this group, nortriptyline elevated the blood alcohol level significantly at both 15 and 45 minutes after alcohol administration (P<0.01).
4. Alcohol plus nortriptyline, 20mg/kg of body weight for 10 days. In this group, nortriptyline elevated also the blood alcohol level significantly at both 15 and 45 minutes after alcohol administration (P<0.01).
5. The blood alcohol level of nortriptyline 20 mg /kg of body weight for 5 days was a little higher than that of nortriptyline for 10 days, but the difference was not significant statistically at both 15 and 45minutes after alcohol administration (V>0.3).
Conclusions
1. Nortriptyline when administered orally in a dose of 10 mg/kg of body weight daily for 5 or 10 days, did not elevate the blood alcohol level significantly at both 15 and 45 minutes after alcohol administration.
2. Nortriptyline when administered orally in a dose of 20 mg/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, but there was no significant difference in the blood alcohol level between the two subgroups in which nortriptyline was administered for 5 and 10 days respectively.
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