미량 아민

Chemical_class = 미량 생성되는 내인성 아민
(뇌 조직 1g당 나노그램(ng) 이하) **미량 아민**(trace amine)은 미량 아민 관련 수용체 1(TAAR1) 작용제의 내인성 그룹이며,quote = Trace Amine Associated Receptor 1 (TAAR1) is a G protein coupled receptor (GPCR) that responds to a wide spectrum of agonists, including endogenous trace amines, ... 따라서 모노아민작동성 신경조절물질이다.s2cid = 10272684 미량 아민은 구조적, 대사적으로 고전적 모노아민 신경전달물질과 관련이 있다. 고전적 모노아민에 비해 이들은 미량으로 존재한다. 미량 아민은 포유류의 뇌와 말초 신경 조직 전체에 걸쳐 이질적으로 분포되어 있으며, 높은 대사율을 보인다. 미량 아민은 모체 모노아민 신경전달물질 시스템 내에서 합성될 수 있지만, 이들 중 일부는 자체의 독립적인 신경전달물질 시스템을 구성할 수 있다는 증거가 있다. 미량 아민은 TAAR1이 공존하는 모노아민 뉴런의 시냅스 틈에서 모노아민 신경전달물질의 양을 조절하는 데 중요한 역할을 한다. 이들은 TAAR1 활성화를 통해 이러한 모노아민 뉴런에 대해 잘 알려진 시냅스 전 암페타민과 유사한 효과를 나타냈다. 구체적으로 뉴런에서 TAAR1을 활성화함으로써 시냅스 틈으로부터 모노아민 신경전달물질의 방출을 촉진하고group="주" 재흡수를 방지하며 활동 전위의 생성을 억제한다.pmc=4724540 펜에틸아민과 암페타민은 사람의 도파민 뉴런에서 유사한 약력학을 보이는데, 두 화합물 모두 소포 모노아민 수송체 2(VMAT2)에서의 유출을 유도하고bibcode = 2011NYASA1216...86Eedition=2nd 비슷한 효능으로 TAAR1을 활성화시키기 때문이다. 도파민, 노르에피네프린, 세로토닌과 마찬가지로 미량 아민은 ADHD,quote = changes in trace amines, in particular PE, have been identified as a possible factor for the onset of attention deficit/hyperactivity disorder (ADHD) [5, 27, 43, 78]. PE has been shown to induce hyperactivity and aggression, two of the cardinal clinical features of ADHD, in experimental animals [100]. Hyperactivity is also a symptom of phenylketonuria, which as discussed above is associated with a markedly elevated PE turnover [44]. Further, amphetamines, which have clinical utility in ADHD, are good ligands at trace amine receptors [2]. Of possible relevance in this aspect is modafanil, which has shown beneficial effects in ADHD patients [101] and has been reported to enhance the activity of PE at TAAR1 [102]. Conversely, methylphenidate, which is also clinically useful in ADHD, showed poor efficacy at the TAAR1 receptor [2]. In this respect it is worth noting that the enhancement of functioning at TAAR1 seen with modafanil was not a result of a direct interaction with TAAR1 [102].
More direct evidence has been obtained recently for a role of trace amines in ADHD. Urinary PE levels have been reported to be decreased in ADHD patients in comparison to both controls and patients with autism [103-105]. Evidence for a decrease in PE levels in the brain of ADHD patients has also recently been reported [4]. In addition, decreases in the urine and plasma levels of the PE metabolite phenylacetic acid and the precursors phenylalanine and tyrosine have been reported along with decreases in plasma tyramine [103]. Following treatment with methylphenidate, patients who responded positively showed a normalization of urinary PE, whilst non-responders showed no change from baseline values [105]. 우울증, 조현병 등 사람의 다양한 정서 및 인지 장애에 영향을 미치는 것으로 알려져 있다.quote = Although the functional role of trace amines in mammals remains largely enigmatic, it has been noted that trace amine levels can be altered in various human disorders, including schizophrenia, Parkinson's disease, attention deficit hyperactivity disorder (ADHD), Tourette syndrome, and phenylketonuria (Boulton, 1980; Sandler et al., 1980). It was generally held that trace amines affect the monoamine system indirectly via interaction with plasma membrane transporters [such as plasma membrane dopamine transporter (DAT)] and vesicular storage (Premont et al., 2001; Branchek and Blackburn, 2003; Berry, 2004; Sotnikova et al., 2004). ...
Furthermore, DAT-deficient mice provide a model to investigate the inhibitory actions of amphetamines on hyperactivity, the feature of amphetamines believed to be important for their therapeutic action in ADHD (Gainetdinov et al., 1999; Gainetdinov and Caron, 2003). It should be noted also that the best-established agonist of TAAR1, β-PEA, shared the ability of amphetamine to induce inhibition of dopamine-dependent hyperactivity of DAT-KO mice (Gainetdinov et al., 1999; Sotnikova et al., 2004).
Furthermore, if TAAR1 could be proven as a mediator of some of amphetamine's actions in vivo, the development of novel TAAR1-selective agonists and antagonists could provide a new approach for the treatment of amphetamine-related conditions such as addiction and/or disorders in which amphetamine is used therapeutically. In particular, because amphetamine has remained the most effective pharmacological treatment in ADHD for many years, a potential role of TAAR1 in the mechanism of the "paradoxical" effectiveness of amphetamine in this disorder should be explored. 미량 아민작동성 저기능은 특히 ADHD와 관련이 있는데, 그 이유는 ADHD 환자의 소변 및 혈장 펜에틸아민의 농도가 대조군에 비해 현저히 낮고, ADHD에 가장 흔히 처방되는 두 가지 약물인 암페타민과 메틸페니데이트는 치료에 반응하는 ADHD 환자의 펜에틸아민 생합성을 증가시키기 때문이다.quote = Although we did not find a sufficient number of studies suitable for a meta-analysis of PEA and ADHD, three studies20,57,58 confirmed that urinary levels of PEA were significantly lower in patients with ADHD compared with controls. ... Administration of D-amphetamine and methylphenidate resulted in a markedly increased urinary excretion of PEA,20,60 suggesting that ADHD treatments normalize PEA levels. ... Similarly, urinary biogenic trace amine PEA levels could be a biomarker for the diagnosis of ADHD,20,57,58 for treatment efficacy,20,60 and associated with symptoms of inattentivenesss.59 ... With regard to zinc supplementation, a placebo controlled trial reported that doses up to 30 mg/day of zinc were safe for at least 8 weeks, but the clinical effect was equivocal except for the finding of a 37% reduction in amphetamine optimal dose with 30 mg per day of zinc.110 ADHD 바이오마커에 대한 체계적 고찰의 결과, 소변의 펜에틸아민 수치가 ADHD 진단 바이오마커가 될 수 있음이 밝혀졌다.
# 미량 아민의 목록
align=right 사람의 미량 아민에는 다음과 같은 것들이 있다. *펜에틸아민(카테콜아민과 관련됨): ** 펜에틸아민quote= Trace amines are metabolized in the mammalian body via monoamine oxidase (MAO; EC 1.4.3.4) (Berry, 2004) (Fig. 2) ... It deaminates primary and secondary amines that are free in the neuronal cytoplasm but not those bound in storage vesicles of the sympathetic neurone ... Similarly, β-PEA would not be deaminated in the gut as it is a selective substrate for MAO-B which is not found in the gut ...
Brain levels of endogenous trace amines are several hundred-fold below those for the classical neurotransmitters noradrenaline, dopamine and serotonin but their rates of synthesis are equivalent to those of noradrenaline and dopamine and they have a very rapid turnover rate (Berry, 2004). Endogenous extracellular tissue levels of trace amines measured in the brain are in the low nanomolar range. These low concentrations arise because of their very short half-life ... (PEA) ** *N*-메틸펜에틸아민 (내인성 암페타민 이성질체) ** 페닐에탄올아민s2cid=10829497doi = 10.1016/j.biopha.2016.07.002 ** *m*-티라민 ** *p*-티라민 ** 3-메톡시티라민 ** *N*-메틸티라민quote=In addition to the main metabolic pathway, TAs can also be converted by nonspecific N-methyltransferase (NMT) [22] and phenylethanolamine N-methyltransferase (PNMT) [23] to the corresponding secondary amines (e.g. synephrine [14], N-methylphenylethylamine and N-methyltyramine [15]), which display similar activities on TAAR1 (TA1) as their primary amine precursors...Both dopamine and 3-methoxytyramine, which do not undergo further N-methylation, are partial agonists of TAAR1 (TA1). ...
The dysregulation of TA levels has been linked to several diseases, which highlights the corresponding members of the TAAR family as potential targets for drug development. In this article, we focus on the relevance of TAs and their receptors to nervous system-related disorders, namely schizophrenia and depression; however, TAs have also been linked to other diseases such as migraine, attention deficit hyperactivity disorder, substance abuse and eating disorders [7,8,36]. Clinical studies report increased β-PEA plasma levels in patients suffering from acute schizophrenia [37] and elevated urinary excretion of β-PEA in paranoid schizophrenics [38], which supports a role of TAs in schizophrenia. As a result of these studies, β-PEA has been referred to as the body's 'endogenous amphetamine' [39] ** 노르페네프린 ** *p*-옥토파민 ** 시네프린other= * 티로나민 화합물: ** 3-아이오도티로나민 * 트립타민doi = 10.1111/j.1471-4159.2010.07109.x 고전적 모노아민인 노르에피네프린, 세로토닌, 히스타민은 그 자체로는 미량 아민이 아니지만 모두 사람의 TAAR1 수용체의 부분 작용제이다. 도파민은 사람의 TAAR1에 대한 높은 친화력을 가지고 있는 작용제이다.quote =Rank order of potency
tyramine > β-phenylethylamine > octopamine = dopamineaccess-date=29 January 2016 *N*-메틸트립타민과 *N*,*N*-다이메틸트립타민은 사람의 내인성 아민이지만, 2015년을 기준으로 이들의 사람의 TAAR1에 대한 결합은 확인되지 않았다.
# 농도
미량 아민은 신경계에 미량 또는 매우 낮은 농도로 존재하기 때문에 이런 이름이 붙여졌다.url = 이러한 농도는 세로토닌, 도파민, 노르에피네프린과 같은 고전적인 모노아민 신경전달물질보다 훨씬 낮다. 그러나 모노아민 산화효소에 대한 강한 민감성에 따른 미량 아민의 빠른 대사 회전율은 이들이 정상 상태 측정으로 예측한 것보다 훨씬 높은 농도로 화학적 시냅스로 존재할 수 있음을 시사한다.
# 역사
이 연구의 역사적 발전을 특히 잘 논의한 미량 아민 관련 수용체에 대한 철저한 검토는 그랜디(Grandy)의 검토이다.doi = 10.1016/j.pharmthera.2007.06.007
# 주해
group=주