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우울증 치료에서 빠른 효과와 적은 부작용을 가진새로운 N-Methyl-D-Aspartate(NMDA) 수용체 길항제

Other N-Methyl-D-Aspartate (NMDA) Receptor Antagonists with a Rapid Onset of Action and Less Side Effect in the Treatment of Depression

이화영|최범성
대한생물정신의학회 (The Korean Society Of Biological Psychiatry)|2015.11|생물정신의학 (Journal of Korean Society of Biological Psychiatry)|제22권 제4호|pp. 149-154

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참고문헌

키워드

Major depressive disorderKetamine케타민Glutamate글루타메이트주요우울증NMDA 수용체 길항제NMDA receptor antagonist
주제분류정신과학

초록

우울증은 환자의 기능에 많은 장애를 유발하며 재발이 잦고, 만성적인 경과를 보이는 질환이다.1-3) 많은 환자들이 우울삽화 사이의 기간에도 잔류 증상을 보이며, 환자의 15~20% 정도는 2년 이상 우울 증상이 지속되는 것으로 알려져 있다.2) 우울증의 원인 규명과 치료제 개발에 많은 노력이 있어왔으며, 지금까지 개발된 항우울제들이 효과가 있지만, 효능과부작용 등에서 부족한 부분이 있다. 다양한 유발요인, 복잡한증상 양상과 경과 등으로 인한 불분명한 신경생물학적 기전등으로 많은 어려움이 있는 실정이다. 우울증의 원인 규명과치료법 개발을 위해 여러 신경생물학적 기전들이 제시되고있다. 단가아민 가설(monoamine hypothesis), 만성 스트레스 가설(chronic stress hypothesis), 신경가소성 가설(neuroplasticity hypothesis), 그리고 후생유전학적 가설(epigenetic hypothesis) 등이 기분장애 발생의 신경생물학적 기전 가설들중에 대표적인 것이다.4) 최근 기분장애의 발생에 중요성이부각이 되고 있는 것이 신경가소성(neuroplasticity)과 세포회복 탄력성(cellular resilience)의 이상이다. 많은 항우울제들이 신경 영양작용(neurotrophic effect)과 신경세포 보호작용(neuroprotective effect)을 통해서 항우울효과를 나타낸다고 보고되고 있다.5) 글루타메이트(glutamate)는 포유류의 중추신경계에서 가장 많이 분포하는 흥분성 신경전달물질(ex-citatory neurotransmitter)이다. 대표적인 억제성 신경전달 물질(inhibitory neurotransmitter)인 gamma-aminobutyric acid (이하 GABA)에 의해서, 글루타메이트에 의해 유발된 흥분성신경전달(signal transduction)이 조절을 받고 있다.6) 그리고흥분신호전달과 억제신호전달의 불균형은 불안장애, 우울증의 발생에도 관련이 있다고 알려져 있다. 여기에는 글루타메이트에 의한 흥분성 신호전달의 증가와 GABA의 억제성 신호전달의 감소가 관여되는 것으로 생각된다. 그리고 뇌와 뇌척수액(cerebrospinal fluid, CSF)에서 글루타메이트의 농도가 우울증 환자에서 정상보다 더 증가되어 있는 것도 관찰되었다.7) 이처럼 글루타메이트 신경전달은 우울증 발생의 병태생리에 중요한 역할을 하고 있으며 다수의 항우울제의 주된작용도 글루타메이트 신경전달을 조절해서 나타난다.8) 글루타메이트 수용체와 관련된 기전을 연구하는 것은 우울증의 기전 및 새로운 항우울제를 개발하는 데 매우 중요하다. 여기에서는 이와 관련된 생물학적인 개념 설명과 새로운항우울제 개발에 관한 최근 연구 결과들을 알아보고 우울증치료에 어떻게 기여하고 있는지를 설명하고자 한다.

Abstract

Mood disorder is a common psychiatric illness with a high lifetime prevalence in the general population. Many prescribed antidepressants modulate monoamine neurotransmitters including serotonin, norepinephrine and dopamine. There has been greater focus on the major excitatory neurotransmitter in the human brain, glutamate, in the pathophysiology and treatment of major depressive disorder (MDD). Recently, ketamine, an N-methyl-D-aspartate receptor antagonist, has received attention and has been investigated for clinical trials and neurobiological studies. In this article, we will review the clinical evidence for glutamatergic dysfunction in MDD, the progress with ketamine as a rapidly acting antidepressant, and other N-methyl-D-aspartate receptor antagonist for treatment-resistant depression.

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