• 제목/요약/키워드: Dopamine $D_4$ receptor

검색결과 73건 처리시간 0.035초

우울증 치료에서 빠른 효과와 적은 부작용을 가진 새로운 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)

  • 최범성;이화영
    • 생물정신의학
    • /
    • 제22권4호
    • /
    • pp.149-154
    • /
    • 2015
  • 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.

한국인 정신분열병 환자에서 항정신병 약물의 치료 반응과 도파민 D2, D3 및 D4 수용체 유전자 다형성 (The Relationship between the Therapeutic Response to Antipsychotic Drugs and the Dopamine D2, D3, and D4 Receptor Gene Polymorphisms in Korean Schizophrenic Patients)

  • 김희철;정성원;김대광;정철호
    • 생물정신의학
    • /
    • 제14권3호
    • /
    • pp.167-176
    • /
    • 2007
  • 항정신병 약물의 치료 반응을 예측해 줄 수 있는 유전자 지표를 찾기 위한 최근의 많은 약물유전학 연구들은 일관된 결과를 보고하지 못하고 있다. 본 연구는 항정신병 약물의 치료 반응과 도파민 D2, D3 및 D4 수용체 유전자 다형성과 관련성을 조사하였다. 연구 대상은 18~60세에 해당되면서 정신분열병의 DSM-IV 진단기준을 만족하고 본 연구에 대해 서면 동의한 국립부곡병원의 입원 환자 200명이었다. 연구는 대상자들의 입원 당시 병록지를 검토하여 후향적으로 이루어졌다. 대상자들은 퇴원할 당시를 기준으로 약물치료 반응 정도에 따라'반응군'과'비반응군'으로 구분되었으며 양군 사이의 도파민 수용체 유전자 다형성 차이를 비교하였다. 대상자 200명 중에서 188명(94%)이 비전형 항정신병 약물을 사용하였고 반응군은 141명(70.5%)이었다. 도파민 D2 수용체 유전자 Ser311Cys 다형성, 도파민 D3 수용체 유전자 Ser9Gly 다형성, 도파민 D4 수용체 유전자 exon III의 48개 염기반복 다형성에서 반응군과 비반응군 사이의 대립유전자 및 유전자형 빈도의 차이를 보이지 않았다. 결론적으로 본 연구에서는 항정신병 약물의 치료 반응과 도파민 D2 수용체 유전자 Ser311Cys 다형성, 도파민 D3 수용체 유전자 Ser9Gly 다형성, 그리고 도파민 D4 수용체 유전자 exon III의 48개 염기반복 다형 성과는 연관성이 없었다. 향후에는 단일의 항정신병 약물에 대한 전향적인 방법의 통제된 연구가 필요하다.

  • PDF

월남전 참전 재향군인에서 도파민 D2 수용체 유전자 다형성과 외상후 스트레스 장애 (D2 Dopamine Receptor (DRD2) Gene Polymorphism and Combat-Related Posttraumatic Stress Disorder in Vietnam Veterans)

  • 이수영;정혜경;김태용;최진희;정문용;소형석;신한상;이시은
    • 대한불안의학회지
    • /
    • 제4권2호
    • /
    • pp.142-147
    • /
    • 2008
  • Objective : Evidence from recent studies supports the role of genetic factors in the development of Posttraumatic Stress Disorder (PTSD). The primary aim of this study is to investigate the association between the dopamine D2 receptor (DRD2) TaqI A polymorphism and PTSD. The second aim is to examine the association between the DRD2 TaqI A polymorphism and clinical symptoms in patients with PTSD. Methods : We recruited 189 Vietnam veterans for participation in this study, among whom 99 were PTSD patients and 90 were control subjects. The presence of the DRD2 TaqI A polymorphism was determined by polymerase chain reaction (PCR). Several standardized research scales were used in the clinical assessment of PTSD, including the Combat Exposure Scale (CES), Clinician Administered PTSD Scale (CAPS), Beck Depression Inventory (BDI), and Clinical Global Impression (CGI). Results : There was no significant difference in the distribution of the DRD2 genotype, frequency and prevalence of the A1 allele, or the frequency of heterozygotes between the patients with PTSD and the controls. In the PTSD group, the patients with the A1 allele (A1A1, A1A2) scored higher on the CAPS-total (p=0.044), CAPS-avoidance symptoms (p=0.016) and BDI (p=0.024) than those without the A1 allele (A2A2). Conclusion : We could not find an association between the dopamine D2 receptor (DRD2) TaqI A polymorphism and PTSD. However, the A1 allele of DRD2 seemsto influence avoidance symptoms in patients with PTSD.

  • PDF

틱장애와 도파민 D2 수용체 유전자와의 연합 연구 (Association Study between Tic Disorder and Dopamine D2 Receptor Gene Polymorphism in Korean Population)

  • 이소영;조인희;김선미;이민수;정한용
    • 생물정신의학
    • /
    • 제13권4호
    • /
    • pp.299-304
    • /
    • 2006
  • Objectives : The purpose of the present study was to investigate whether the TaqI A polymorphism of dopamine receptor D2 gene(DRD2) is associated with Tourette syndrome(TS) and chronic motor tic disorder(CMT) in Korean population. Methods : DRD2 TaqI A RFLP genotyping was carried out with DNA extracted from blood samples of 75 patients with tic disorders(47 with TS and 28 with CMT) and 90 healthy subjects. Genotype and allelic frequencies for the DRD2 gene polymorphisms of the tic disorder group as a whole were compared to those of the control group. Separating the TS group, thereafter, the frequency of genotypes and alleles were compared to those of the controls. Results : The results demonstrated that genotype and allele distributions for the DRD2 gene polymorphism in the tic disorder as a whole, TS, and control groups were not significantly different. Conclusion : No association was found for DRD2 gene, TS and CMT. The data suggest that DRD2 gene may not be a useful marker for the prediction of the susceptibility of tic disorder.

  • PDF

약물유전체학과 정신분열병 (Pharmacogenomics and Schizophrenia)

  • 이규영;정인원
    • 생물정신의학
    • /
    • 제8권2호
    • /
    • pp.208-219
    • /
    • 2001
  • The pharmacotherapy of schizophrenia exhibits wide inter-individual variabilities in clinical efficacy and adverse effects. Recently, human genetic diversity has been known as one of the essential factors to the variation in human drug response. This suggests that drug therapy should be tailored to the genetic characteristics of the individual. Pharmacogenetics is the field of investigation that attempts to elucidate genetic basis of an individual's responses to pharmacotherapy, considering drug effects divided into two categories as pharmacokinetics and pharmacodynamics. The emerging field of pharmacogenomics, which focuses on genetic determinants of drug response at the level of the entire human genome, is important for development and prescription of safer and more effective individually tailored drugs and will aid in understanding how genetics influence drug response. In schizophrenia, pharmacogenetic studies have shown the role of genetic variants of the cytochrome P450 enzymes such as CYP2D6, CYP2C19, and CYP2A1 in the metabolism of antipsychotic drugs. At the level of drug targets, variants of the dopamine $D_2$, $D_3$ and $D_4$, and 5-$HT_{2A}$ and 5-$HT_{2C}$ receptors have been examined. The pharmacogenetic studies in schizophrenia presently shows controversial findings which may be related to the multiple involvement of genes with relatively small effects and to the lack of standardized phenotypes. For further development in the pharmacogenomics of schizophrenia, there would be required the extensive outcome measures and definitions, and the powerful new tools of genomics, proteomics and so on.

  • PDF

N-(4-[$^{18}F$Fluoromethylbenzyl)spiperone : 유력한 도파민 $D_2$ 수용체 선택성 방사성리간드 (N-(4-[$^{18}F$]Fluoromethylbenzyl)spiperone : A Selective Radiotracer for In Vivo Studies of Dopamine $D_2$ Receptors)

  • 김상은;최연성;지대윤;이경한;최용;김병태
    • 대한핵의학회지
    • /
    • 제31권4호
    • /
    • pp.421-426
    • /
    • 1997
  • [$^{18}F$]FMBS는 도파민 $D_2$ 수용체 방사성추적자로서 유망한 성질을 지니고 있다. [$^{18}F$]FMBS는 비교적 높은 특이결합/비특이결합 비를 제공하며, 그 체내결합은 도파민 $D_2$ 수용체에 대하여 높은 특이성과 선택성을 보인다. 도파빈 $D_2$ 수용체 측정을 위한 보다 적합한 PET 방사성추적자를 얻기 위해서는 [$^{18}F$]FMBS의 낮은 뇌섭취와 느린 역학을 개선할 수 있는 화학적 구조의 변형이 시도되어야 하며, [$^{18}F$]FMBS는 이러한 시도의 골격이 될 수 있을 것으로 믿는다.

  • PDF

말에서 Dopamine Receptor D4 유전자의 변이 특성 분석 (Characterization of Dopamine Receptor D4 Gene Polymorphisms in Horses)

  • 최재영;최연주;이종안;신상민;윤민중;강용준;신문철;유지현;김현아;조인철;양병철;김남영
    • 생명과학회지
    • /
    • 제32권1호
    • /
    • pp.29-35
    • /
    • 2022
  • 본 연구는 여러 말 품종에서 Dopamine Receptor D4 (DRD4)의 유전적 다형성 및 Jeju crossbred에서의 기질특성과의 연관성을 분석하였다. DRD4 유전자의 다형성은 인간을 포함한 다양한 포유동물에서 기질과 연관된 후보 유전자이다. 말의 DRD4의 엑손 3번 영역에 있는 SNP G292A는 Thoroughbred에서 호기심과 경계와 관련이 있는 것으로 보고 되었다. 세 가지 말 품종에서 DRD4 유전자 내 존재하는 변이들의 다형성을 확인하기 위해 Sanger sequencing을 활용하였다. 제주마에서 각각의 빈도는 타 품종과 큰 차이를 보였다. 말의 품성 평가는 Jeju crossbred를 이용하여 수행하였으며, 기질 평가와 접촉 평가를 활용하여 각각 5개 항목과 2개 항목을 점수화 하였다. 품성 평가 결과 각 항목 간의 높은 상관관계를 확인하였다. 말의 DRD4 유전자 내 변이와 품성 평가 결과를 비교한 결과 대립유전자 A를 가지고 있을 때 기질 평가 5개 항목에서 모두 점수가 낮은 경향을 보이는 것을 확인하였으나 유의성은 없었다. Jeju crossbred의 G292A의 SNP과 혈액 내 도파민 수치를 비교한 결과 GA형이 GG형보다 약 2.87배 높은 결과를 확인하였다. 이번 연구를 통하여 DRD4 유전자 다형성과 말의 기질을 평가하기 위한 여러 평가 방법 및 신경전달물질과의 연관성을 확인할 수 있었다. 추가적인 연구를 통하여 품성 평가를 위한 유전자 마커로서 활용 가능할 것으로 사료된다.

Synaptic Concentration of Dopamine in Rat Striatal Slices in Relationship to $[^3H]$Raclopride Binding to the Dopamine $D_2$ Receptor

  • Park, Mi-Hwa;Park, Eun-Hee
    • Archives of Pharmacal Research
    • /
    • 제23권4호
    • /
    • pp.360-366
    • /
    • 2000
  • The in vivo binding of dopamine (DA) radioligands to $D_2$receptors can be affected by competition with endogenous dopamine. In the present study, we used a brain slice preparation that provides more controlled conditions than in vivo preparations in order to examine the relationship between synaptic DA and the binding of [$^3H$] raclopride to $D_2$receptors. We also estimated the synaptic DA concentration in rat striatal slices by determining the changes in [$^3H$] raclopride binding. To correlate the changes in [$^3$H]raclopride binding with the concentration of synaptic DA, the kinetic parameters were determined. [$^3H$] Raclopride reached equilibrium binding conditions within two hours. The K value for DA in inhibiting [$^3$H]raclopride binding was about 2.2 nM. The increase in synaptic DA evoked by electrical stimulation decreased the striatal binding of [$^3H$] raclopride in a frequency-dependent manner. Increases in the DA concentration evoked by amphetamine (AMPH) or cocaine decreased [$^3H$] raclopride binding by 74% or 20%, respectively, corresponding to increases in the synaptic DA concentrations of 1.6 nM or 0.6 nM, respectively. Pargyline also decreased [$^3H$] raclopride binding by 36%corresponding at a concentration of 1.2 nM. In contrast, the depletion of synaptic DA by $\alpha$-methyl-p-tyrosine ($\alpha$-MpT) increased the specific binding of [$^3H$] raclopride by 43%when the DA concentration was decreased to 0.7 nM. The changes in the DA concentration at the synapse were responsible for the changes in the striatal binding of [$^3H$] raclopride. The values calculated in this study may therefore approximate the changes in the synaptic DA concentration in rat striatal slices following manipulation.

  • PDF

한국인 알코올중독 환자의 예후인자에 관한 연구 : 심리적, 사회적, 생물학적 요인을 중심으로 (A Study for The Prognostic Indicators of Korean Alcoholics in Psychological, Social and Biological Aspects)

  • 성상경;장환일
    • 생물정신의학
    • /
    • 제2권2호
    • /
    • pp.218-236
    • /
    • 1995
  • The author studied prognostic indicators of sixty Korean male alcoholics in psychological, social and biological aspects who were divided into abstinent and drinking groups. Thirty patients were assigned to each group. They were controlled in age and sex. Both groups were compared in terms of the demographic characteristics, past drinking history, treatment history, famaily history, ego strength and personality factors differences and distribution of dopamine $D_2$ receptor gene Al allele. Also the author studied relation of clinical course, alcoholic family history and dopamine $D_2$ receptor gene Al allele in both groups. The results were as follows; 1) The abstinent group had higher rate of married state, higher economic status, longer education years and maintained more stable job than the drinking group. But made no differences in occupation and religion. 2) The abstinent group showed higher rate of living with family members than the drinking group, and wives and fellows of the alcoholics anonymous were important factors for maintenance of abstinence. Family loading and parent's characters were not different. 3) The abstinent group had longer maximal length of abstinence but mean amount of alcohol consumption per day were larger than the drinking group. But there were no differences in duration of past drinking, drinking pattern, main drinking time, first drinking age and preference of the kind of alcoholic beverage in the past drinking history. 4) The abstinent group showed stronger treatment motivation, absolute abstinence in treatment goal, more voluntary adimission and maintained longer therapeutic relationship otter discharge than the drinking group. But both groups showed negative attitude toward antabuse therapy. 5) The abstinent group had higher mean score in ego strength scale than the drinking group. 6) In the personality factor questionnaire, the abstinent group showed strong laugh poise and the trait of praxernia, conservatism personality but the drinking group showed tough poise, the trait of weak ego strength(unstableness) and tough mindedness personality. 7) In comparision of dopamine $D_2$ receptor gene A1 allele, the prevalence of A1 allele was seventy percent and the frequency was 0.38 in the abstinent group. The prevalence of A1 allele was sixty percent and the frequency was 0.42 in the drinking group. Both groups were not significantly different in A1 allele prevalence and frequency. 8) In comparision of dopamine $D_2$ receptor gene A1 allele according to alcoholic family history, the prevalence of A1 allele was seventy percent and the frequency was 0.43 in the family history positive group. The prevalence of A1 allele was sixty-one percent and the frequency was 0.38 in the family history negative group. Both groups were not significantly different in A1 allele prevalence and frequency. In comparision of past drinking history according to alcoholic family history, the family history positive group showed earlier first drinking and problem drinking, but the family history negative group hod longer duration of past drinking. The mean amount of alcohol consumption per day, the longest duration of abstinence and Alcoholism Screening Test of Seoul Natoinal Mental Hospital(NAST) results were not significant. In conclusion, the results suggest that successful prognostic indicators of Korean alcoholics are married state, higher economic status, longer education years, stable job, living with family members, longer abstinence during past drinking history, strong treatment motivation, absolute abstinence in treatment goal, voluntary adimission, maintained therapeufic relationship, strong ego strength and the trait of praxernia, conservatism personality. But occupation, religion, alcoholic family history, parent's characters, duration of past drinking, drinking pattern, main drinking time, first drinking age, preference of the kind of alcoholic beverage, attitude to antabuse therapy and distribution of dopamine $D_2$ receptor A1 allele were not significantly related to the prognostic indicators of Korean alcoholics.

  • PDF

저용량의 Haloperidol투여에 의해 유발된 백서 뇌내 Dopamine $D_2$양 수용체증식 (Proliferation of Dopamine $D_2$-Like Receptors after Treatment with Low Dose Haloperidol in Rat Brain)

  • 김황진;한규희
    • 생물정신의학
    • /
    • 제3권2호
    • /
    • pp.240-244
    • /
    • 1996
  • 흰쥐에 항정신병약물인 haloperidol을 장기간 투여한 뒤 줄무늬체와 후결절 조직에서의 DA $D_2$양 수용체의 변동에 대해 조사하였다. 약물투여군 4군에게 haloperidol을 각기 0.05, 0.15, 0.5, 1.5mg/kg/day이 되게끔 4주간 투여하였다. DA수용체의 변동은 [$^3H$]spiperone을 이용한 결합반응법을 통해 알아 보았다. 정상대조군에 비해 4주 동안 haloperidol을 투여받은 군 모두에서 줄무늬체에서의 DA 수용체의 최대 결합치가 증가한 것으로 나타났다. 기존의 연구에서 사용한 용량보다 대단히 낮은 0.05mg/kg/day을 투여받은 군 역시 유의한 증가를 보여 낮은 용량의 haloperidol이 DA계에 영향을 미치는 것을 알 수 있었다. 후결절조직의 최대결합치는 haloperidol투여군 모두에서 증가한 경향을 볼 수 있었으나 정상대조군에 비해 1.5mg/kg/day투여군에서 유의한 증가를 볼 수 있었다. 본 실혐의 결과로 미루어 낮은 용량의 haloperidol을 장기간 투여했을 때 뇌내 DA계에 수용체증식이 나타나며 항정신병 효과의 발현과도 관련성이 시사된다. 이러한 결과는 최근 거론되고 있는 항정신병약물의 저용량투여를 간접적으로 지지하는 것으로 생각되며 DA계의 연동을 알리는 다른 생물학적 지표와의 관련성을 살피면 흥미로운 결과를 얻을 것으로 기대된다.

  • PDF