트레이스 아민

Trace amine
트레이스 아민
마약류
Chemical structure diagrams
페네틸아민 해골
클래스 식별자
작용기전수용체 작용제
생물학적 표적인간 추적 아민 관련 수용체 1
케미컬 클래스미량발생 내생아민
(뇌조직의 그램 당 나노그램 이하)
외부 링크
메슈C434723
위키다타에서

미량아민은 미량아민 관련 수용체 1(TAAR1) 작용제의[1] 내생성 집단으로, 구조적으로나 대사적으로 고전적인[2][3][4] [5]모노아민 신경전달물질과 관련이 있다. 기존의 모노아민에 비해 미량농도로 존재한다.[5] 그들은 포유류의 뇌와 말초신경조직 전체에 이질적으로 분포하며 신진대사의 비율이 높다.[5][6] 부모 모노아민 신경전달물질 시스템 내에서 합성할 수 있지만,[7] 이들 중 일부는 독자적인 신경전달물질 시스템으로 구성될 수 있다는 증거가 있다.[2]

트레이스 아민은 공동 국소화된 모노아민 뉴런의 시냅스 구획에서 모노아민 신경전달물질의 양을 조절하는데 중요한 역할을 한다.[6] 그들은 TAAR1 활성화를 통해 이러한 모노아민 뉴런에 대한 잘 알려진 사전 시냅스 암페타민 같은 효과를 가지고 있다;[3][4] 특히, 뉴런에서 TAAR1을 활성화함으로써 뉴런 발화를 억제할 뿐만 아니라 시냅스 구획으로부터 모노아민 신경전달물질의 방출을[note 1] 촉진하고 재흡수를 방지한다.[6][8] 페네틸아민과 암페타민은 사람 도파민 뉴런에서 두 화합물이 모두 베시픽 모노아민 전달체 2([7][9]VMAT2)에서 유출을 유도하고 비교 가능한 효능으로 TAAR1을 활성화하기 때문에 유사한 약물역학성을 가지고 있다.[6]

도파민, 노르에피네프린, 세로토닌과 마찬가지로, 미량아민은 ADHD,[3][4][10] 우울증[3][4],[2][3][4] 조현병과 같은 영향과 인식의 광범위한 인간 장애에 관련되어 있다.[3][4][10] 미량 아미노기 저자극은 특히 ADHD와 관련하여 비뇨기 및 혈장 페네틸아민 농도가 ADHD 개인과 ADHD, 암페타민 및 메틸페니데이트에 대해 가장 일반적으로 처방되는 두 가지 약물이 ADHD 개인에서 현저히 낮기 때문에 ADHD와 관련이 있으며, A를 가진 치료 반응 개인에서 페네틸아민 생합성을 증가시킨다.DHD.[3][11] ADHD 바이오마커에 대한 체계적인 검토 결과, 비뇨기 페네틸아민 수치가 ADHD에 대한 진단 바이오마커일 수 있음을 알 수 있었다.[11]

미량아민 목록

인간 뇌에[12][13][14] 있는 카테콜아민과 미량아민의 생체합성 경로
The image above contains clickable links
페네틸아민성 미량아민(노란색으로 표시)과 카테콜아민(catecholamines)은 아미노산L-페닐알라닌에서 유래한다.

인간 추적 아민은 다음을 포함한다.


아민 자체를 추적하지는 않지만 고전적인 모노아민스 노레피네프린, 세로토닌, 히스타민 등은 모두 인간 TAAR1 수용체에서 부분작용제, 도파민은 인간 TAAR1에서 고선호작용제다.[6][8][17][18]N-메틸트립타민과 N-디메틸트립타민은 인간의 내인성 아민이지만, 2015년 현재 인간 TAAR1 결합은 결정되지 않았다.[2]

역사

이 연구의 역사적 진화를 특히 잘 논하는 미량적 아민 관련 수용체에 대한 철저한 검토가 그란디의 그것이다.[19]

참고 항목

메모들

  1. ^ 특정 미량아민(예: 페네틸아민)은 기능상 베실러 모노아민 전달체 VMAT2를 억제하는 반면, 다른 미량아민(예: 문어민)은 기능상 억제한다. 모노아민 뉴런에서 VMAT2 기능을 억제하지 않는 트레이스 아민은 신경전달물질을 효과적으로 방출하지 않는다.

참조

  1. ^ Panas MW, Xie Z, Panas HN, Hoener MC, Vallender EJ, Miller GM (December 2012). "Trace amine associated receptor 1 signaling in activated lymphocytes". J Neuroimmune Pharmacol. 7 (4): 866–76. doi:10.1007/s11481-011-9321-4. PMC 3593117. PMID 22038157. 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, ...
  2. ^ a b c d Burchett SA, Hicks TP (August 2006). "The mysterious trace amines: protean neuromodulators of synaptic transmission in mammalian brain". Prog. Neurobiol. 79 (5–6): 223–46. doi:10.1016/j.pneurobio.2006.07.003. PMID 16962229. S2CID 10272684.
  3. ^ a b c d e f g Berry MD (January 2007). "The potential of trace amines and their receptors for treating neurological and psychiatric diseases". Rev Recent Clin Trials. 2 (1): 3–19. doi:10.2174/157488707779318107. PMID 18473983. 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].
  4. ^ a b c d e f g h i j k Lindemann L, Hoener MC (May 2005). "A renaissance in trace amines inspired by a novel GPCR family". Trends Pharmacol. Sci. 26 (5): 274–281. doi:10.1016/j.tips.2005.03.007. PMID 15860375. 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]
  5. ^ a b c d e f g h i j Broadley KJ (March 2010). "The vascular effects of trace amines and amphetamines". Pharmacol. Ther. 125 (3): 363–375. doi:10.1016/j.pharmthera.2009.11.005. PMID 19948186. 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 ...
  6. ^ a b c d e f g h Miller GM (January 2011). "The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity". J. Neurochem. 116 (2): 164–176. doi:10.1111/j.1471-4159.2010.07109.x. PMC 3005101. PMID 21073468.
  7. ^ a b Eiden LE, Weihe E (January 2011). "VMAT2: a dynamic regulator of brain monoaminergic neuronal function interacting with drugs of abuse". Ann. N. Y. Acad. Sci. 1216 (1): 86–98. Bibcode:2011NYASA1216...86E. doi:10.1111/j.1749-6632.2010.05906.x. PMC 4183197. PMID 21272013. [Trace aminergic] neurons in mammalian CNS would be identifiable as neurons expressing VMAT2 for storage, and the biosynthetic enzyme aromatic amino acid decarboxylase (AADC).
  8. ^ a b Grandy DK, Miller GM, Li JX (February 2016). ""TAARgeting Addiction"-The Alamo Bears Witness to Another Revolution: An Overview of the Plenary Symposium of the 2015 Behavior, Biology and Chemistry Conference". Drug Alcohol Depend. 159: 9–16. doi:10.1016/j.drugalcdep.2015.11.014. PMC 4724540. PMID 26644139. TAAR1 is a high-affinity receptor for METH/AMPH and DA
  9. ^ Offermanns, S; Rosenthal, W, eds. (2008). Encyclopedia of Molecular Pharmacology (2nd ed.). Berlin: Springer. pp. 1219–1222. ISBN 978-3540389163.
  10. ^ a b Sotnikova TD, Caron MG, Gainetdinov RR (August 2009). "Trace amine-associated receptors as emerging therapeutic targets". Mol. Pharmacol. 76 (2): 229–35. doi:10.1124/mol.109.055970. PMC 2713119. PMID 19389919. 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.
  11. ^ a b Scassellati C, Bonvicini C, Faraone SV, Gennarelli M (October 2012). "Biomarkers and attention-deficit/hyperactivity disorder: a systematic review and meta-analyses". J. Am. Acad. Child Adolesc. Psychiatry. 51 (10): 1003–1019.e20. doi:10.1016/j.jaac.2012.08.015. PMID 23021477. 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
  12. ^ Broadley KJ (March 2010). "The vascular effects of trace amines and amphetamines". Pharmacology & Therapeutics. 125 (3): 363–375. doi:10.1016/j.pharmthera.2009.11.005. PMID 19948186.
  13. ^ Lindemann L, Hoener MC (May 2005). "A renaissance in trace amines inspired by a novel GPCR family". Trends in Pharmacological Sciences. 26 (5): 274–281. doi:10.1016/j.tips.2005.03.007. PMID 15860375.
  14. ^ Wang X, Li J, Dong G, Yue J (February 2014). "The endogenous substrates of brain CYP2D". European Journal of Pharmacology. 724: 211–218. doi:10.1016/j.ejphar.2013.12.025. PMID 24374199.
  15. ^ a b c d e f g h i j k l Khan MZ, Nawaz W (October 2016). "The emerging roles of human trace amines and human trace amine-associated receptors (hTAARs) in central nervous system". Biomed. Pharmacother. 83: 439–449. doi:10.1016/j.biopha.2016.07.002. PMID 27424325.
  16. ^ Wainscott DB, Little SP, Yin T, Tu Y, Rocco VP, He JX, Nelson DL (January 2007). "Pharmacologic characterization of the cloned human trace amine-associated receptor1 (TAAR1) and evidence for species differences with the rat TAAR1". The Journal of Pharmacology and Experimental Therapeutics. 320 (1): 475–85. doi:10.1124/jpet.106.112532. PMID 17038507. S2CID 10829497.
  17. ^ Maguire JJ, Davenport AP (19 July 2016). "Trace amine receptor: TA1 receptor". IUPHAR/BPS Guide to PHARMACOLOGY. International Union of Basic and Clinical Pharmacology. Retrieved 22 September 2016. Rank order of potency
    tyramine > β-phenylethylamine > octopamine = dopamine
  18. ^ "Dopamine: Biological activity". IUPHAR/BPS guide to pharmacology. International Union of Basic and Clinical Pharmacology. Retrieved 29 January 2016.
  19. ^ Grandy DK (December 2007). "Trace amine-associated receptor 1-Family archetype or iconoclast?". Pharmacol. Ther. 116 (3): 355–90. doi:10.1016/j.pharmthera.2007.06.007. PMC 2767338. PMID 17888514.