痕量胺
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痕量胺（英文：Trace amine）是一类与经典的生物胺（如儿茶酚胺类、血清素、组胺）结构类似的内源性物质，包括p-酪胺、β-苯乙胺、色胺、章胺和类甲腺质，存在于动物（昆虫至哺乳动物）的神经系统中。痕量胺屬於TAAR1激動劑[1]，因此也是单胺能神经调节剂[2][3][4]，在結構及機能上類似单胺类神经递质[5]，但相較於經典的生物胺，痕量胺在生物體內的濃度相當低[5]。
| 痕量胺 | |
|---|---|
| 药物种类 | |
 苯乙胺結構圖 | |
| 生物靶标 | 人類 TAAR1 |
| 外部链接 | |
| MeSH | C434723 |
參考資料 编辑
- ^ Panas MW, Xie Z, Panas HN, Hoener MC, Vallender EJ, Miller GM. Trace amine associated receptor 1 signaling in activated lymphocytes. J Neuroimmune Pharmacol. December 2012, 7 (4): 866–76. PMC 3593117
. PMID 22038157. doi:10.1007/s11481-011-9321-4. 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, ...
- ^ Burchett SA, Hicks TP. The mysterious trace amines: protean neuromodulators of synaptic transmission in mammalian brain. Prog. Neurobiol. August 2006, 79 (5–6): 223–46. PMID 16962229. doi:10.1016/j.pneurobio.2006.07.003.
- ^ Berry MD. The potential of trace amines and their receptors for treating neurological and psychiatric diseases. Rev Recent Clin Trials. January 2007, 2 (1): 3–19. PMID 18473983. doi:10.2174/157488707779318107.
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]. - ^ Lindemann L, Hoener MC. A renaissance in trace amines inspired by a novel GPCR family. Trends Pharmacol. Sci. May 2005, 26 (5): 274–281. PMID 15860375. doi:10.1016/j.tips.2005.03.007.
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] - ^ 5.0 5.1 Broadley KJ. The vascular effects of trace amines and amphetamines. Pharmacol. Ther. March 2010, 125 (3): 363–375. PMID 19948186. doi:10.1016/j.pharmthera.2009.11.005.
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 ...
