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Trace Amines and Their Relevance to Psychiatry and Neurology: a Brief Overview Deepak Narang, Bsc1, Sara Tomlinson, Bsc 2, Andrew Holt, Phd1, Darrell D

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Trace Amines and Their Relevance to Psychiatry and Neurology: a Brief Overview Deepak Narang, Bsc1, Sara Tomlinson, Bsc 2, Andrew Holt, Phd1, Darrell D Gözden Geçirmeler / Reviews DOI: 10.5350/KPB-BCP201121113 Trace Amines and Their Relevance to Psychiatry and Neurology: A Brief Overview Deepak Narang, BSc1, Sara Tomlinson, BSc 2, Andrew Holt, PhD1, Darrell D. Mousseau, PhD3, Glen B. Baker, PhD, DSc, FCAHS2 ÖZET: ABS TRACT: Eser aminler ve psikiyatri ve nöroloji ile ilişkisi: Trace amines and their relevance to psychiatry Kısa bir gözden geçirme and neurology: a brief overview Arilalkilaminler β-feniletilamin, m- ve p-tiramin, triptamin, The arylalkylamines, β-phenylethylamine, m- and m- ve p-oktapamin, feniletanolamin ve sinefrin klasik p-tyramine, tryptamine, m- and p-octopamine, amin nörotransmitterler olan noradrenalin, dopamin ve phenylethanolamine and synephrine, have been termed 5-hidroksitriptamin (5-HT, serotonin)’e oranla santral sinir trace amines because of their low absolute concentrations sistemindeki mutlak konsantrasyonlarının düşük olması in the central nervous system relative to the classical nedeniyle eser aminler olarak adlandırılmıştır. Düşük kon- neurotransmitter amines, noradrenaline, dopamine and santrasyonlarda bulunmalarına rağmen bu aminler bir çok 5-hydroxytryptamine (5-HT, serotonin). Despite being psikiyatrik ve nörolojik hastalığın etyolojisi ve farmakote- present at low concentrations, these amines have been rapisinde yer alırlar. Eser aminlerle ilgili çalışmalar 1970’ler implicated in the etiology and pharmacotherapy of several 1Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada ve 1980’lerde kapsamlı elektrofizyolojik çalışmalar ve bazı psychiatric and neurological disorders. Studies on trace 2Department of Psychiatry, University of Alberta, Edmonton, Alberta, Canada reseptör bağlanma çalışmaları ile birlikte bu aminler için amines flourished in the 1970s and 1980s, following the 3Department of Psychiatry, University of duyarlı testlerin gelişmesinden sonra artmıştır. Geçtiğimiz development of sensitive assays for these amines, and Saskatchewan, Saskatoon, Saskatchewan, Canada son on yılda bu aminlere olan ilgi, G-proteini ile çalışan were accompanied by comprehensive electrophysiological reseptör ailesinin keşfi ve klonlanması ile canlanmıştır, studies and some receptor binding studies. There has Ya zış ma Ad re si / Add ress rep rint re qu ests to: Glen B. Baker, Neurochemical Research Unit, bunlardan bazıları eser aminlerle seçici olarak aktive olma- been a resurgence of interest in these amines in the Department of Psychiatry, 12-105B Clinical Sciences Building, University of Alberta, sı nedeniyle eser aminle ilişkili reseptörler (trace amine past decade with the discovery and cloning of a unique Edmonton, AB, Canada T6G 2G3. associated receptors (TAARs)) olarak adlandırılmıştır. Bu family of G-protein-coupled receptors, some of which are Telefon / Phone: (780)-492-5994 reseptörlerin eser aminlerin etkisi ile ve diğer birçok nöro- selectively activated by trace amines; these receptors have kimyasal ve psikotropik ilaçlarla ilişkisi tartışılmıştır. been termed trace amine, associated receptors (TAARs). Elekt ro nik pos ta ad re si / E-ma il add ress: [email protected] The relevance of these receptors to the actions of the trace Ka bul ta ri hi / Da te of ac cep tan ce: Anahtar sözcükler: Eser aminle ilişkili reseptörler, amines and to the actions of several other neurochemicals 20 Şubat 2011 / February 20, 2011 β-feniletilamin, tiramin, oktapamin, triptamin, psikiyat- and psychotropic drugs is discussed. rik ve nörolojik hastalıklar Bağıntı beyanı: D.N., S.T., A.H., D.D.M., G.B.B.: Yazarlar bu Key words: Trace amine-associated receptors, makale ile ilgili olarak herhangi bir çıkar Kli nik Psi ko far ma ko lo ji Bül te ni 2011;21:73-79 β-phenylethylamine, tyramine, octopamine, tryptamine, çatışması bildirmemişlerdir. psychiatric and neurological disorders Declaration of interest: D.N., S.T., A.H., D.D.M., G.B.B.: The authors reported no conflict of interest related to Bulletin of Clinical Psychopharmacology 2011;21:73-79 this article. INTRODUCTION epilepsy and migraine headaches [review books and articles: (1-8)]. These amines are related structurally to, Since the 1960s, there has been considerable interest in but present in the brain at much lower concentrations than, the so-called trace amines in the central nervous system the classical neurotransmitter amines dopamine (DA), (CNS) because of their possible involvement in a number noradrenaline (NA) and 5-hydroxytryptamine (5-HT, of psychiatric and neurological disorders, including serotonin), and include ß-phenylethylamine (PEA), depression, schizophrenia, phenylketonuria (PKU), tryptamine (T), phenylethanolamine (PEOH), m- and Reye’s syndrome, Parkinson’s disease, attention deficit p-tyramine (TA), m- and p-octopamine (OA) and hyperactivity disorder (ADHD), Tourette’s syndrome, synephrine (SYN) [some authors include N,N- Klinik Psikofarmakoloji Bülteni, Cilt: 21, Sayı: 1, 2011 / Bulletin of Clinical Psychopharmacology, Vol: 21, N.: 1, 2011 - www.psikofarmakoloji.org 73 Trace amines and their relevance to psychiatry and neurology: a brief overview Figure 1: Chemical structures of trace amines and classical neurotransmitter amines. dimethyltryptamine (DMT) in this list]. See Figure 1 for of the trace amines (10-14). Although research on the trace structures of these trace amines. This brief review will amines decreased in the 1990s, there has been a resurgence focus on PEA, TA, OA and T. of interest in these amines following reports in 2001 of the During the 1970s and 1980s, the development of a discovery of a novel family of G protein-coupled receptors, number of sensitive analytical techniques which facilitated some of which appeared to be selectively activated by trace the measurement of trace amines in the brain and body amines (15,16). fluids (1) resulted in extensive research on the bioavailability, The trace amines can alter the release and/or reuptake distribution and function of trace amines. Comprehensive of NA, DA and/or 5-HT (17,18), not only by regulating the electrophysiological and behavioral research was also active transport of these neurotransmitters across the conducted (1,3,5-7), and the findings suggested that these plasma membrane, but also by involving mechanisms of amines might act as neuromodulators for DA, NA and/or action targeting the neurotransmitter vesicles themselves. 5-HT [although there is strong evidence for OA being a Electrophysiological studies have revealed that several neurotransmitter in invertebrates (3,6,9)]; however, not all trace amines can also potentiate the actions of these of the results ascribed to trace amines could be accounted classical monoamine neurotransmitters by altering the for by simple neuromodulatory mechanism(s) and this sensitivity of their receptors; such findings have led some conclusion was subsequently supported by binding studies researchers to propose that one role of trace amines is to that suggested the existence of specific receptors for some maintain the activity of NA, DA and/or 5-HT within 74 Klinik Psikofarmakoloji Bülteni, Cilt: 21, Sayı: 1, 2011 / Bulletin of Clinical Psychopharmacology, Vol: 21, N.: 1, 2011 - www.psikofarmakoloji.org D. Narang, S. Tomlinson, A. Holt, D. D. Mousseau, G. B. Baker defined physiological limits (1,4,5,19,20). Interestingly, both glutamatergic and GABAergic systems (5). PEA can also stimulate acetylcholine release through Brain levels of trace amines have been reported to be activation of glutamatergic signaling pathways (21), and altered by several drugs used to treat neuropsychiatric PEA and p-TA have been reported to depress GABAB disorders. Administration of monoamine oxidase (MAO) receptor-mediated responses in dopaminergic neurons inhibitor antidepressants such as phenelzine and (22,23). Although PEA, T and p-TA have been reported to tranylcypromine results in a greater increase in brain be present in synaptosomes (nerve ending preparations levels of trace amines than of classical neurotransmitter isolated during homogenization and centrifugation of amines (1, 54). In addition, chronic administration of PEA brain tissue) (24), research with reserpine and neurotoxins to rats produces a ß-adrenoceptor down-regulation similar suggests that m- and p-TA may be stored in vesicles while to that observed with some antidepressants (56), while PEA and T are not (25-27). In a comprehensive review reserpine depletes central levels of some trace amines (54), paper, Burchett and Hicks (28) have provided a review of and the antidepressant effects of exercise have been the regional brain distribution of the trace amines and their suggested to be due to an elevation of PEA (57). l-Deprenyl localization relative to catecholaminergic and serotonergic (selegiline), a selective inhibitor of MAO-B, is used in the neuronal systems in the brain and have suggested four treatment of Parkinson’s disease and produces a marked kinds of trace amine activity in the CNS: co-transmitters increase in brain levels of PEA relative to other amines released with the catecholamines or 5-HT; transmitters (20,58). In rodents, acute administration of the with their own receptors; false transmitters at catecholamine antipsychotics chlorpromazine, fluphenazine and receptors; and neuromodulators. haloperidol has been shown to decrease striatal p-TA levels, and similar studies with PEA have shown that these antipsychotics increase the rate of accumulation of this INVOLVEMENT OF TRACE trace amine in the striatum (59,60). AMINES IN THE ETIOLOGY OF PSYCHIATRIC AND TRACE AMINE-ASSOCIATED
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