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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
초록· 키워드
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Salsolinol, a dopamine-derived tetrahydroisoquinoline, is one of the endogenous alkaloids structurally related to morphine. It
has been implicated in the pathophysiology of alcohol dependence and Parkinson’s disease since it’s first discovery in 1970’s.
Salsolinol is involved in many neurophysiological processes, including modulation of dopamine activity, facilitation of prolactin
release and reinforcement of additive substance craving. In addition, salsolinol exerts highly neurotoxic effects on dopaminergic
neurons ultimately leading to apoptosis, which is mediated by inhibition of endogenous antioxidants and, thereby, production of
reactive oxygen species (ROS). These properties are considerably based in alcohol dependence and several neurodegenerative
disorders including Parkinson’s disease. Salsolinol is synthesized by the condensation of dopamine with acetaldehyde or pyruvate
through enzymatic or non-enzymatic processes in the dopamine-rich neurons. Acute alcohol ingestion increase the level of
acetaldehyde and salsolinol is structurally related to endogenous opioids. Therefore, it has been suggested that salsolinol may be
the missing link between alcohol ingestion and the activation of reward pathway in the mesolimbic brain. The reinforcing effect
of both alcohol and salsolinol in self-administration setting also strongly supports this hypothesis. N-methylsalsolinol, the major
metabolite of salsolinol, is highly neurotoxic and responsible for the selective destruction of dopaminergic neurons in Parkinson’s
disease. In contrast to this, several structural analogs of salsolinol act as endogenous anti-parkinsonism substances. Delicate structural
differences may underlie this peculiar properties. It may become possible to introduce fine structural modifications, even
stereo-specific manipulations, to develop entirely newer kinds of antiparkinsonism drugs. Although the implication of salsolinol
in the pathophysiology of alcohol dependence had been suggested long ago, the progression of the related research was at most
very limited up to now. Even now, this important chemical, deeply involved in a wide range of essential neurophysiological
processes, still is relatively neglected by psychiatric researchers. However, it is expected that the accumulating knowledge of
salsolinol’s neuromodulatory and neurotoxic effects will give new insights into the many dopamine related psychiatric disorders
including substance dependence, parkinsonism and schizophrenia. We expect that many psychiatrists will give proper attention
to this highly promising research subject. (J Korean Neuropsychiatr Assoc 2008;47(3):217-224)
목차
등록된 정보가 없습니다.
참고문헌 (22)
참고문헌 신청
[학술지(정
Akao Y / 2002 / Mitochondrial permeability transition medicated apoptosis induced by N-methyl(R)salsolinol, and endogenous neurotoxin, and is inhibited by Bcl-2 and rasagili
Chavez-Lara B / 1989 / Pharmacologic study of dopamine catabolites on the contractility of isolated guinea pig myocardium / Arch Inst Cardiol Mex 59 : 367 ~ 373
Cohen G / 1970 / Alkaloids from catecholamines in adrenal tissue: possible role in alcoholism / Science 167 : 1749 ~ 1751
Dringen R / 2003 / Glutathione pathways in the brain / Biol Chem 384 : 505 ~ 516
Akao Y / 2002 / Mitochondrial permeability transition medicated apoptosis induced by N-methyl(R)salsolinol, and endogenous neurotoxin, and is inhibited by Bcl-2 and rasagili
Chavez-Lara B / 1989 / Pharmacologic study of dopamine catabolites on the contractility of isolated guinea pig myocardium / Arch Inst Cardiol Mex 59 : 367 ~ 373
Cohen G / 1970 / Alkaloids from catecholamines in adrenal tissue: possible role in alcoholism / Science 167 : 1749 ~ 1751
Dringen R / 2003 / Glutathione pathways in the brain / Biol Chem 384 : 505 ~ 516
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