Berry M D
Department of Chemistry, Brandon University, 270, 18th Street, Brandon, Manitoba, Canada, R7A 6A9.
Rev Recent Clin Trials. 2007 Jan;2(1):3-19. doi: 10.2174/157488707779318107.
Mining of the human genome has revealed approximately 7000 novel proteins, which could serve as potential targets for the development of novel therapeutics. Of these, approximately 2000 are predicted to be G-protein coupled receptors. Within this group of proteins, a family of 18 mammalian receptors has recently been identified that appear to exhibit selectivity toward the so-called trace amines. The trace amines are a family of endogenous compounds with strong structural similarity to classical monoamine neurotransmitters, consisting primarily of 2-phenylethylamine, m- and p-tyramine, tryptamine, m- and p-octopamine and the synephrines. The endogenous levels of these compounds are at least two orders of magnitude below those of neurotransmitters such as dopamine, noradrenaline and 5-HT. The effects of these low physiological concentrations have been difficult to demonstrate but it has been suggested that they may serve to maintain the neuronal activity of monoamine neurotransmitters within defined physiological limits. Such an effect of trace amines would make them ideal candidates for the development of novel therapeutics for a wide range of human disorders. Although the demonstration of a trace amine family of receptors has seen a resurgence of interest in these endogenous compounds, with recent articles reviewing trace amine pharmacological and physiological responses, the potential clinical utility of the trace amine receptors has not been specifically addressed. Historically, trace amines have been implicated in a diverse array of human pathologies ranging from schizophrenia to affective disorders to migraine. Recent studies have strengthened some of this historical data by linking trace amine receptor polymorphisms and mutations to distinct clinical conditions. The aim of the current article is to review the previous studies linking trace amines to human pathology in the context of the recently discovered trace amine receptors and evidence of the existence of trace amine receptor polymorphisms and mutations associated with such disorders. In addition, recent evidence linking trace amines to the development of drug dependence will be discussed.
对人类基因组的挖掘发现了大约7000种新蛋白质，它们可能成为新型疗法开发的潜在靶点。其中，大约2000种预计为G蛋白偶联受体。在这组蛋白质中，最近发现了一个由18种哺乳动物受体组成的家族，它们似乎对所谓的痕量胺具有选择性。痕量胺是一类内源性化合物，与经典单胺神经递质具有很强的结构相似性，主要包括2-苯乙胺、间酪氨酸和对酪氨酸、色胺、间去甲肾上腺素和对去甲肾上腺素以及辛弗林。这些化合物的内源性水平比多巴胺、去甲肾上腺素和5-羟色胺等神经递质至少低两个数量级。这些低生理浓度的作用难以证明，但有人认为它们可能有助于将单胺神经递质的神经元活性维持在确定的生理限度内。痕量胺的这种作用将使它们成为开发治疗多种人类疾病的新型疗法的理想候选物。尽管痕量胺受体家族的发现重新引发了人们对这些内源性化合物的兴趣，最近有文章综述了痕量胺的药理和生理反应，但痕量胺受体的潜在临床应用尚未得到具体探讨。从历史上看，痕量胺与从精神分裂症到情感障碍再到偏头痛等一系列人类病理状况有关。最近的研究通过将痕量胺受体多态性和突变与不同的临床状况联系起来，加强了其中一些历史数据。本文的目的是在最近发现的痕量胺受体以及与这些疾病相关的痕量胺受体多态性和突变存在证据的背景下，回顾以前将痕量胺与人类病理联系起来的研究。此外，还将讨论最近将痕量胺与药物依赖发展联系起来的证据。
