Effects of nitrazepam on blood alcohol level in rabbits

의학과/석사[한글] Nitrazepam은 1,4 -benzodiazepine계 수면제로서 현재 임상에서 널리 사용되고 있다. 향정신성 약물을 복용하는 환자들에서 음주로 인한 사고의 위험이 증가하고 있기 때문에, 주정과의 상호작용을 알아보는 것이 중요하며, 급만성 주정 중독환자의 치료에 어떤 약물을 선택할 것인가 하는 점은 중요한 관심사가 되어 왔다. 이러한 사실에서 ni-trazepam이 가토 혈중 주정농도에 미치는 영향을 규명해 봄은 이론적으로나 실제적으로 의의가 있을 것으로 보아 본 연구를 시행하였다. 실험재료 및 실험방법 1. 실험동물은 체중 2.0㎏ 내외의 성숙 자웅 가토를 사용하였다. 2. 비교군에서는 주정만 단독 투여하였다. 3. 실험군은 다음과 같이 4아군으로 구분하였다. 1) 주정 + nitrazepam 1일 5㎎/㎏ 연 5일 투여군 2) 주정 + nitrazepam 1일 5㎎/㎏ 연 10일 투여군 3) 주정 + nitrazepam 1일 10㎎/㎏ 연 5일 투여군 4) 주정 + nitrazepam 1일 10㎎/㎏ 연 10일 투여군 4. 주정투여는 20% ethanol 용액을 체중 매 ㎏당 5.0㎖를 이변 정맥내로 5분간에 걸쳐 서서히 정맥 주사하였다. 5. 채혈은 주정 투여후 15분과 45분에 심장 천자로 시행하였다. 6. 주정의 쳔중 농도는 Cavett씨 방법에 의해 측정하였다. 실험결과 1. Nitrazepam을 1일 5㎎/㎏씩 연 5일 투여시, 주정투여 후 15분 및 45분에서 각기 혈중 주정농도에 유의한 변화가 없었다. 연10일간 투여시 주정투여 후 15분 및 45분 모두에서 혈중 주정농도가 유의하게 높았다. 2. Nitrazepam 1일 10㎎/㎏씩 연 5일 투여시, 주정투여 후 15분 및 45분에서 각기 혈중 주정농도에 유의한 변화가 없었다. 연10일간 투여시 주정투여 후 15분 및 45분 모두에서 혈중 주정농도가 유의하게 높았다. [영문] Nitrazepam is one of 1.4-benzodiazepine derivatives widelyused as a hypnotic In clinical medicine. Chemically it is 1,3-dihydro-7-nitro-5-phenyl-2H-1, 4-benzodiazepie-2-one. The sedative and anticonvulsant effects of nitrazepam on experimental animals resemble those of other benzodiazeplnes. It also proved to be effective in the treatment of enuresis. But it is used as a safe and potent hypnotic rather than as an anxiolytic agent . Investigators suggested that any new psychotropic drugs should be tested for their Interaction with alcohol, because they might precipitate rusk in case of consuming them concurrently. In view of these facts, the author conducted an animal experiment to investigate the effects of nitrazepam on b1ood alcohol level in rabbits. Material and Method 1. The experimental work was done on mature rabbits of both serves, weighing about 2Kg. 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 4 subgroups : a) Nitrazepam 5㎎/㎏/day for 5days plus alcohol b) Nitrazepam 5㎎/㎏/day for 10days plus alchol c) Nltrazepam 10㎎/㎏/day for 5day plus alcohol d) Nltrazepam 10㎎/㎏/day for 10day plus alchol 5. Nltrazepam was given orally in a single dally dose at the fluted tome. The Last dose was given one hour and a half before alcohol admintstration. 6. In all froups, 20% ethanol solution was slowly given in a dose of 5.O㎖/㎏ of body weight for 5 minutes by intravenous route. 7. ALL of the blood specimens were obtained by cardiac puncturn at both 15 and 45 minutes after alcohol admlnlstratlon. 8. The blood alcohol level was determind by Cavett's method. Results 1. Nitrazepam 5㎎/㎏/day for 5days plus alcohol Nitrazepam did not change the blood aIcohol level significantly at both L5 and 45 minutes after alcohol administrataion. (p > 0.6 > 0.1, respectively) 2. Nitazepam 5㎎/㎏/day for 10days plus alcohol. In this group, nitrazepam elevated the blood alcohol level significantly at both 15 and 45 minutes after alcohol administration. (p > 0.001 ,< 0.001, respectively) 3. Nitrazepam 10㎎/㎏/day for 5days plus alcohol. In this group, there was also no significant change in the blood level at both 15 and 45 minutes after alcohol admiuistrataion. (p > 0.05, > 0.05, respectively) 4. Nitrazepam 10㎎/㎏/day for 10days plus alcohol. In this group, nitrazepam elevated the blood alcohol level significantly at both 15 and 45 minutes after alcohol administration. (p > 0.01 > 0.001, respectively) Conclusion 1. Nitrazepam, when administered orally in a dose of 5㎎/㎏ of body weight dally for 5days net change the blood alcohol level significantly at both 15 and 45 minutes after alcohol administration. But nitrazepam, when a administered orally in the same dose dally for 10days, elevated the blood alcohol level significantly at both 15 and 45 minutes after alcohol administration. 2. Nitrazepam, when administered orally in a dose of 10㎎/㎏ of body weight dally for 5days did not change the blood alcohol level significantly at both 15 and 45 minutes after alchol administration. But, nitrazepam, when administered orally in the same dose daily for 10days, elevated the blood alcohol level significantly at both 15 and 45 minutes after alcohol administration.restrictio

Effect of tricyclic antidepressants on the levels of biogenic amines and their metabolites in rat brain

의학과/박사[한글] 삼환 항우울제 투여로 뇌수의 biogenic amine황성이 항진된다는 것은 대체로 인정되나, 대부분의 실험이 뇌조직 전체 또는 어느 한 부위를 대상으로 하고 또한 특정 amine만을 검색하여 전반적인 뇌기능을 유기적으로 추구하지 못하고 있는 실정이다. 이번 실험에서는 삼환 항우울제인 imipramine 및 desipramine을 일회 또는 장기간 흰쥐에 투여하여 뇌내 biogenic amine과 그 대사산물의 함량변동을 관찰하였다. 동일한 실험동물에서 뇌척수액과 뇌의 부위별 조직 (전두피질, 선조체, 해마, 시상, 시상하부, 혹질, 소뇌)을 적출하여 norepinephrine, epinephrine, dopamine 및 5-hydroxytryptamine (5-HT) 과 대사산물인 dihydroxyphenylacetic acid(DOPAC), homovanillic acid(HVA) 및 5-hydroxyindoleacetic acid(5-HIAA ) 를 High Performance Liquid Chromatography·Electrochemical Detector(HPLC-ECD)로 측정하고 상호 연관성을 검색하였다. 실험성적을 요약하면 다음과 같다. 1. 정상 흰쥐의 뇌조직내 norepinephrine 단위함량은 시상하부에서 가장 높았으며 dopamine, DOPAC 및 HVA는 선조체에서, 5-HT와 5·HIAA는 흑질에서 가장 높았고 epinephrine은 어느 부위에서도 검출되지 않았다. 2. Imipramine 일회투여로 시상하부, 선조체, 전두피질, 혹질 및 시상에서 5·HIAA 함량이 감소되었고, 선조체의 DOPAC 함량도 감소되었다. 장기투여로는 biogenic amino 및 대사산물함량이 대조군과 비슷하였으나 선조체의 DOPAC 함량은 감소되었다. 3. Desipramine 일회투여로는 뇌내 biogenic amine 및 대사산물 함량변동이 경미하나 전두피질에서 5·HIAA 함량이, 선조체에서 DOPAC 함량이 감소되었다. 장기투여로는 시상, 해마, 흑질, 전두피질, 시상하부에서 norepinephrine 함량이 감소하였으며 선조체에서 DOPAC 함량이 감소되었다. 4. 뇌척수액에서는 5·HIAA와 HVA 만이 검출되었으며 imipramine 또는 desipramine투여로 변동이 없었다. 이상의 성적으로 보아 삼환 항우울제 투여에 의한 뇌내 biogenic amine 함량변동은 투여약물 및 뇌의 부위에 따라 다르나, imipramine은 5-HT에, desipramine은 norepinephrine에 주로 영향을 주어 항우울 작용에 관계하고, 또한 선조체의 dopamine 대사감소도 항우울 작용에 일부 관여된다고 생각한다. [영문] It is generally accepted that the activity of biogenic amines is affected by tricyclic antidepressants. However, since most studies were performed on whole brain or limited area of brain and measured only specific monoamines, changes in the levels of biogenic amines in discrete brain regions or difference between the regions might have been masked. Present investigation was undertaken to elucidate the effect of acute or chronic treatment with tricyclic antidepressants on the regional levees of biogenic amines in brain and cerebrospinal fluid. The male Sprague-Dawley fats were used. After single or 3 weeks'treatment with imipramine or desipramine, blocks of tissue were obtained from the frontal cortex, corpus striatum, hippocampus, thalamus, hypothalamus, substance nigra and cerebellum immediate after collection of cerebrospinal fluid from cisterna magna. The concentration of biogenic amines and their metabolites(norepinephrine, epinephrine, dopamine, 5-hydfoxytryptamine (5-HT), dihydroxyphenylacetic acid(DOPAC), homovanillic acid(HVA), 5-hydroxyindoleacetic acid (5-HIAA)in brain tissues and cerebrospinal fluid were measured by means of High Performance Liquid Chromatography-Electroshemical Detector(HPLC-ECD). The results obtained are as follows. 1. In the brain of normal rat, the concentration of norepinephrine was the highest in hypothalamus and those of dopamine, DOPAC, and HVA were the highest in corpus striatum, and those of 5-HT and 5-HIAA were the highest in substantia nigra. Epinephrine was not detectable in any part of the brain tissues nor in cerebrospinal fluid. 2. Single administration of imipramine decreased the concentration of 5-HIAA in hypo-thalamus, corpus striatum, frontal cortex, substantia nigra and thalamus, and that of DOPAC in corpus striatum. Chronic imipramine treatment decreased the concentration of DOPAC only in corpus striatum. 3. Single administration of desipramine decreased the concentration of 5-HIAA in frontal cortex and that of DOPAC in corpus striatum. Chronic desipramine treatment decreased the concentration of norepinephrine in thalamus, hippocampus, substantia nigra, frontal cortex and hypothalamus, and that of DOPAC in corpus striatum. 4. In cerebrospinal fluid only 5-HIAA and HVA were detectable and the concentration of these metabolites were not changed by the treatment with imipramine or desipramine. These results indicate that the effects of single or chronic treatment with the tricyclic antidepressants on the biogenic amines and their metabolites differ to the regions of rat brain. And it is conceived that the treatment with imipramine affects mainly 5-HT metabolism, and that with desipramine affect mainly norepinephrine metabolism, and at least in part, decreased metabolism of dopamine in corpus striatum contributes to the antidepressant effeCt of these drugs.restrictio