China
Africa
Explore chapters and articles related to this topic
Pharmacotherapy of Neurochemical Imbalances
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Rupali Patil, Aman Upaganlawar, Suvarna Ingale
Many substances of different chemical nature are identified as neurotransmitters. Depending upon their chemical nature, neurotransmitters are classified into five groups: Amino Acids: These neurotransmitters mediate fast synaptic transmission and functions as inhibitory and excitatory in nature. Examples include GABA, glycine, glutamate, and aspartate (Ayano, 2016).Amines: These are chemically transformed amino acids. They mediate slow synaptic transmission. These also functions as inhibitory and excitatory in action. Examples include NA, adrenaline, DA, serotonin, and histamine (Ayano, 2016).Trace Amines: For example, phenethylamine, N-methylphenethylamine, tyramine, 3-iodothyronamine, octopamine, tryptamine, etc.Peptides: For example opioid peptides, substance P, etc.Purines: For example adenosine triphosphate (ATP), adenosine, etc.
Diseases of the Nervous System
Published in George Feuer, Felix A. de la Iglesia, Molecular Biochemistry of Human Disease, 2020
George Feuer, Felix A. de la Iglesia
The function of these trace amines is related to the monoaminergic system. The mode of action of these compounds involves the process of neurotransmission acting directly or indirectly. They are synthetized in the cytoplasm of the neuron, interact with synaptic membranes, and produce continuous activation. This activation creates a synaptic potential responsible for the synapsic transmission. Any imbalance in the amount of trace amines caused by enzyme defects, altered membrane permeability, presence of drugs or toxic compounds, or dietary changes may be involved in the onset of some neurological and psychiatric illnesses. Some of these amines are behaviorally active with abnormal amounts excreted in parkinsonism, affective disorders, schizophrenia, migraine, and hepatic and renal coma.148,232,265,334,501 The administration of phenylalanine and a phenylalanine hydroxylase inhibitor to pregnant rats increased the octopamine/noradrenaline ratio in the fetal brain from 2:1 to 13:1. Octopamine is elevated in hepatic failure, which may be linked to neurological symptoms. The hypothalamic levels of octopamine are 12 times higher in children who died of acute hepatic encephalopathy or Reye’s syndrome.357 Octopamine may act as a false neurotransmitter in these liver diseases. The enzyme responsible for the methylation of these amines is present in platelets; the activity of the platelet enzyme shows differences in various mental disorders. There is a significant increase in schizophrenic patients both in acute and chronic conditions, and it is also elevated in affective disorders or slightly reduced in alcoholics.
Update on novel antipsychotics and pharmacological strategies for treatment-resistant schizophrenia
Published in Expert Opinion on Pharmacotherapy, 2022
Andrea de Bartolomeis, Mariateresa Ciccarelli, Licia Vellucci, Michele Fornaro, Felice Iasevoli, Annarita Barone
Trace amine-associated receptor 1 (TAAR1) is a G-protein-coupled receptor identified in several tissues including the olfactory epithelium and the central nervous system [139]. TAAR1 is activated by endogenous trace amines (Figure 1), which are structurally related to monoamines, such as serotonin and dopamine [140]. Trace amines are considered potential neuromodulators, since β-phenylethylamine and p-tyramine have been shown to modify the release and/or response to dopamine, norepinephrine, acetylcholine, and GABA [141]. TAAR1 interaction with D2R reduces the recruitment of β-arrestin 2, thereby silencing the GSK3β cascade via Akt [151]. Of interest, this intracellular pathway converges on the downstream targets activated by mood stabilizers, such as lithium. This peculiar feature of TAAR1 agonists could provide a novel therapeutic strategy for schizophrenia compared to current pharmacological standards [139].
Trace amine associated receptor 1 (TAAR1) expression and modulation of inflammatory cytokine production in mouse bone marrow-derived macrophages: a novel mechanism for inflammation in ulcerative colitis
Published in Immunopharmacology and Immunotoxicology, 2019
Katlynn Bugda Gwilt, Neva Olliffe, Rachel A. Hoffing, Gregory M. Miller
Owing to previous reports that TAAR1 activation can elicit chemotactic responses from immune cells [8], we propose that TAAR1 may be acting as an integrator of dietary and microbiomic signals. As outlined in Figure 5, TYR originating in the lumen of the GIT, either originating from consumed food or secreted by the microbiota, has the potential to transgress the epithelial barrier and cause an increase in production of proinflammatory gene expression in macrophages. This increase in proinflammatory cytokine gene expression will recruit peripheral immune cells, as well as further activates both tissue and infiltrating macrophages to the site of inflammation. Babusyte et al. demonstrate that polymorphonuclear cells chemotax toward trace amines as nanomolar affinities [8], and preliminary data outlined from our lab confirms these findings (data not shown). As previously demonstrated, TYR levels are elevated in the fecal content of patients with UC. Linares et al. have previously shown cytotoxic effects of TYR on colon epithelial cells in vitro, but to date, there have been no studies on the effects of TYR on BMDM. Due to the high levels of TYR in the lumen of the GIT, infiltrating immune cells may chemotax toward biogenic amines in the lumen promoting breakdown of the tight junctions as they permeate the epithelial cell barrier. Accordingly, we hypothesize that the use of TAAR1 antagonists (or partial agonists) would attenuate this feed-forward mechanism in the lumen, potentially serving as a novel therapeutic approach to attenuate inflammation while reducing the need for intensive monoclonal anti-TNFα therapies.
Trace amine-associated receptor 1: a multimodal therapeutic target for neuropsychiatric diseases
Published in Expert Opinion on Therapeutic Targets, 2018
Michael D. Schwartz, Juan J. Canales, Riccardo Zucchi, Stefano Espinoza, Ilya Sukhanov, Raul R. Gainetdinov
The trace amines, endogenous amines closely related to the biogenic amine neurotransmitters (e.g. dopamine (DA), serotonin (5-hydroxytryptamine; 5-HT) and norepinephrine (NE)), have been known to exert physiological and neurological effects since the early twentieth century [1]. However, the lack of an identifiable endogenous receptor for these molecules, coupled with their markedly low in vivo concentrations, led in part to the idea that trace amines were ‘false neurotransmitters’ [2]. In 2001, this conventional wisdom was challenged with the identification of a vertebrate G-protein coupled receptor (GPCR) that preferentially responded to trace amines [3,4]. This receptor, trace amine-associated receptor 1 (TAAR1), is part of a large and evolutionarily diverse family of TAARs with six functional members in humans [5]. Several TAARs act as olfactory receptors [6]. In the mammalian brain, the finding that TAAR1 powerfully modulates monoaminergic neurotransmission [7–9] has rejuvenated research efforts into the function and therapeutic implications of TAAR1 and its ligands.