Ephedrine이 뇌내 biogenic amine 함량에 미치는 영향

Abstract

[영문]

[한글]

Ephedrine은 임상적으로 일부 천식, 비염 치료에 이용되고 부작용으로 불안, 초조 및

불면증등의 신경증상과 심한 경우에는 정신병을 일으키기도 한다. 이러한 신경증상이나

정신병의 유발에는 뇌내의 여러 신경전달 물질의 변동이 관계되고, 또한 ephedrine과 유

사한 작용과 구조를 가진 methamphetamine이나 amphetamine에 의해서도 신경 전달물질의

변동이 나타나므로 ephedrine에 의한 신경증이나 정신병에도 이런 여러 뇌내의 biogenic

amine이 관계될 것이라 생각된다. 그러나 말초 작용에 대하여서는 거의 연구가 이루어지

지 않은 실정이다. 이번 실험에서는 흰쥐에 ephedrine을 1회 혹은 1일 2회씩 5일간 반복

투여한 후에 여러 뇌조직 (전두피질, 선조체, 해마, 시상, 시상하부, 흑질, 소뇌)에서 no

repinephrine, epinephrine, dopamine 및 5-hydroxytryptamine과 대사산물인 3,4-dihydro

xyphenylacetic acid (DOPAC), homobanillic acid (HVA) 및 5-hydroxyindoleacetic acid

(5-HIAA)를 high performance liquid chromatography-electrochemical detector (HPLC-EC

D)로 측정하여 biogenic amine의 함량변동과 대사변동 양상을 관찰하여 ephedrine에 의한

중추 흥분효과와 신경전달 물질간의 상호 연관성을 검색하였다.

실험 결과를 요약하면 다음과 같다.

1. 정상 흰쥐에 있어서 norepinephrine 단위 함량은 시상하부에서 가장 높으며, dopami

ne, DOPAC 및 HVA는 선조체에서, 5-HT와 5-HIAA는 흑질에서 가장 높고, epinephrine은 어

느 부위에서도 검출되지 않았다.

2. Ephedrine을 1회 투여하면 선조체의 DOPAC 함량이 감소한 것 이외에는 별다른 변동

을 나타내지 않았다.

3. Ephedrine을 반복 투여하면 뇌의 모든 부위에서 norepinephrine이 감소하였다. Dopa

mine은 선조체와 흑질에서 감소되었고 시상하부에서 증가하였으며, HVA는 선조체에서 감

소되었다. 5-HT는 소뇌를 제외한 모든 부위에서 감소되었고, 5-HIAA는 전두피질에서만 감

소를 나타내었으나, 5-HIAA/5-HT는 선조체, 시상, 시상하부 및 흑질에서 증가되었다.

이상의 성적으로 보아 ephedrine 1회 투여로는 신경전달 물질의 변동을 일으키지 않으

나 반복 투여하면 norepinephrine 및 5-HT의 감소를 일으켜 중추신경계의 기능이상을 초

래할 수 있다고 생각된다.

Effect of Ephedrine on the Levels of Biogenic Amines and Their Metabolites in Rat

Brain

Kyung Eun Lee

Department of Medical Science The Graduate School Yonsei University

(Directed by Professor Sa Suk Hong, M.D.)

Sympathomimetic amines, especially ephedrine, are a major ingredient in

proprietary medications for symptomatic treatment of upper respiratory infections.

Their frequent uses can lead to occasional instances of abuse and habituation.

The clinical symptoms of ephedrine abuse are similar to that of amphetamine

psychosis and resemble closely that of schizophrenia. Because both amphetamine

psychosis and schizophrenia are thought to be mediated primarily through the action

on catecholamines, ephedrine-induced changes of the biogenic amines can be

suspected.

However, there were few studies about the central effects of ephedrine because of

the milder central action than eripheral.

Therefore, the present investigation was undertaken to elucidate the relations

between the effects of single or repeated administration of ephedrine on the

regional levels of biogenic amines in rat brain and ephedrine-induced CNS

stimulation. The male Sprague-Dawley rats weighing 100-200g were used. After single

or repeated administrations of ephedrine, blocks of tissue were obtained from

frontal cortex, corpus striatum, hippocampus, thalamus, hypothalamus, substantia

nigra and cerebellum. The concentration of biogenic amines (norepinephrine,

ephedrine, dopamine, 5-hydroxytryptamine (5-HT)) and their metabolites

(3,4-dihydroxytryptamine liquid chromatography - electrochemical detector

(HPLC-ECD).

The results obtained were as follows:

1. In the normal rat, the concentration of norepinephrine was the highest in

hypothalamus. Dopamine, DOPAC and HVA were highest in corpus striatum, and 5-HT and

5-HIAA were highest in substantia nigra. Epinephrine was not deteCTAble in aly part

of the brain tissue.

2. In a single administration of ephedrine, the concentration of DOPAC was

decreased in corpus striatum.

However, the other biogenic amines and their metabolites were not changed.

3. In repeated administration of ephedrine, the concentration of norepinephrine

was decreased in all brain region checked.

Dopamine was decreased in corpus striatum and substantia nigra and, increased in

hypothalamus, and HVA was decreased in corpus striatum. 5-HT was decreased in all

brain region except cerebellum and, 5-HIAA was decreased only in frontal cortex.

The ratio of 5-HIAA/5-HT was increased in corpus striatum, thalamus, hypothalamus

and substantia nigra.

These data indicated that, although a single administration of ephedrine did not

change the central neurotransmitters, repeated administration of ephedrine caused

the decreases of norepinephrine and 5-HT in the most regions of brain, which may be

responsible for the emergence of abnormal behavioral effect after ephedrine abuse.