알코올 의존과 파킨슨병 병태생리에서의 살소리놀(Salsolinol) (Salsolinol in the Pathophysiology of Alcohol Dependence and Parkinson’s Disease)

서지정보

· 발행기관 : 대한신경정신의학회
· 수록지 정보 : 신경정신의학 / 47권 / 3호 / 217 ~ 224페이지
· 저자명 : 정인원, 정성훈, 김진영

초록

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)

영어초록

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)

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