Amines neurotransmitters

Numerous reports of altered neurotransmitter and hormone functions which have been associated with the affective disorders are reviewed by Levell [142]. It was originally proposed that one or more of the neurotransmitter amines in the brain (norepinephrine, dopamine, serotonin) may be functionally elevated in manic patients and reduced in depressed patients [143]. For instance, an increase in the production of dopamine, observed in a number of case reports, is thought to be the cause of the switch into the manic phase in bipolar patients. For example, Bunney et al. reported an increase in the level of homovanillic acid (HVA), a... 

The numerous effects of Li+ upon the neurotransmitters [146,147] and their membrane receptors [148] have been reviewed recently. Li+ affects processes involved with the synthesis of, release of, reuptake of, and receptor activation by neurotransmitters in both animals and humans. In terms of the neurotransmitter amines, serotonin appears to be most affected by Li+, whereas the effects upon dopamine and norepinephrine are small. 

Lovell, R. A., and Freedman, D. X. (1976) Stereospecific receptor sites for d-lysergic acid diethylamide in rat brain Effects of neurotransmitters, amine antagonists and other psychotropic drugs. Mol. Pharmacol., 12 620-630. 

Monoamine oxidase (MAO) is a mammalian flavin-containing enzyme that catalyzes oxidation of primary amines. While the neurotransmitter amines are... 

Biogenic amines are of great interest to researchers because of their potential roles in several psychiatric and neurological disorders. They include dopamine (DA), noradrenaline (NA), 5-hydroxytryptamine (5-HT, serotonin), histamine, and trace amines such as 2-phenylethylamine (PEA), tyramine, octopamine, phenylethanolamine, and tryptamine (Coutts and Baker, 1982). Although GC assays for DA, NA, and 5-HT are available, HPLC analysis with electrochemical detection has for many years now been the method of choice for analysis of these neurotransmitter amines. 

Yamada N, Takahashi S, Todd KG, Baker GB, Paetsch PR. 1993. Effects of two substituted hydrazine monoamine oxidase (MAO) inhibitors on neurotransmitter amines, y-aminobutyric acid, and alanine in rat brain. J Pharm Sci 82 934. 

Monoamine oxidase exists in the human body in two molecular forms, known as type A and type B. Each of these isozymes has selective substrate and inhibitor characteristics. Neurotransmitter amines, such as norepinephrine and serotonin, are preferentially metabolized by MAO-A in the brain. MAO-B is more likely to be involved in the catabolism of human brain dopamine, although dopamine is also a substrate for MAO-A. 

Other studies have shown that the fluorinated drug attains longer-lasting and more consistent concentrations in brain than does TCP. This might result in lowering the clinical dose and hence might also reduce the incidence of side effects apparently contributed to the action of TCP on uptake and release of neurotransmitter amines [57-63], However, comparisons of effects of TCP and FTCP on uptake and release of these amines in vivo and ex vivo in brain and heart will be necessary to clarify this situation. 

Hyland K, Surtees RAH, Rodeck C, Clayton PT (1992) Aromatic 1 amino acid decarboxylase deficiency clinical features, diagnosis and treatment of a new inborn error of neurotransmitter amine synthesis. Neurology 42 1980-1988... 

It is remarkable that a bacterial Na+-coupled proline transporter is more homologous to a mammalian amino acid (or glucose transporter) than are the Na+-depend-ent amino acid transport systems to NaCl-coupled amino acid transporters. The diversity of the ion requirement from a single Na+ to three different ion requirements for transport of some neurotransmitter amines argues for an adaption of a biologically successful mechanism to achieve specialized functions with enhanced sensitivity and selectivity. 

Figure 2 Sites of actions of antidepressants at the synapse (presynaptic nerve terminal, postsynaptic nerve cell, and synaptic cleft between the two are shown). MAO is present in mitochondria, and the shaded circles represent synaptic vesicles that contain neurotransmitter amines.

Monoamine oxidases are flavoproteins that contain one molecule of FAD per molecule. There are two major types of monoamine oxidase (A and B), whose relative concentration varies in tissues of the same species. In general, the A form of the enzyme is more active with endogenous neurotransmitter amines (serotonin, norepinephrine, and epinephrine), whereas the B form is more active toward xenobiotic amines such as 2-phenethylamine. 

Within the lateral and ventromedial hypothalamus the neurotransmitter amines norepinephrine (NE), dopamine (DA) and serotonin (5-HT) play a complex synergistic role in the regulation of food intake and energy expenditure (Meguid et al. 2000). In the lateral hypothalamus of laboratory animals, increased release of NE and DA is associated with inhibition of feeding, whereas in the ventromedial hypothalamus it is associated with stimulation of feeding. By contrast, release of 5-HT in the ventromedial hypothalamus is associated with inhibition of feeding. 

Neuronal projections from the hypothalamus to other regions of the brain relay important output information that influence blood pressure, appetite, thirst, circadian rhythm, behavior, nociception (pain perception), and others factors. Although many of these neurons release neurotransmitter amines at synapses, some of them are known to release neurotransmitter peptides. These include, among others, peptides that closely resemble hormones formed in the gastrointestinal system as well as the endogenous opiates (Table 31-3). 

Trimethoxyphenethylamine similar structure to neurotransmitter amines. One of a number of alkaloids found in the peyote cactus... 

At this point Brodie formulated his unifying hypothesis that serotonin and NE were responsible for controlling brain function and that mental illness might be a consequence of a chemical imbalance in central neurotransmitter amines. The stage was thus set for the medicinal chemist to design molecules which would affect brain amine levels in such a way as to alter the emotional state. 

Monoamine Oxidases (MAO) There are two MAO isoforms, MAO A and MAO B, both of which are flavoen-zymes that oxidize a wide array of neurotransmitter amines. However, they can also biotransform some xenobiotics. Both MAO isoforms consist of approximately 520 amino acid residues and share approximately 70% sequence identity. Their molecular weights are about 58K Daltons. Both isoforms are expressed in most tissues, though not necessarily in equivalent amounts. More MAO is found in liver and placenta, and least in the spleen. Actually MAO-B is... 

This flavoprotein, which catalyzes the oxidative deamination of amines, functions in the breakdown of endogenously produced neurotransmitter amines. Vertebrate monoamine oxidase also catalyzes the oxidation of xenobiotic amines, particularly in tissues such as the intestine (4). Whether the schistosome enzyme is also capable of metabolizing xenobiotics has not been investigated. 

MAO inhibitor tranylcypromine, for example, has been used since the 1960s as an antidepressant. A problem associated with many MAO inhibitors is that they are notoriously nonselective and can interfere with the metabolism of other neurotransmitters, amines found in certain foods, and exogenously administered amine-containing therapeutic agents. 

Patients who do not respond to the tricyclic anti-depressants have two alternative therapies available, both of which increase the availability of neurotransmitter amines in the brain. The monoamine oxidase inhibitors (Section 9.4, p. 359) are highly effective but impose dietary restraints and have often caused dangerous surges in blood-pressure. Electroconvulsive therapy, which may sound brutal, but is actually painless to the patient, can achieve lasting improvement (Green, Heale and Grahame-Smith, 1977). 

Colombian poison dart frogs are tiny, beautiful, and deadly. They produce a poison called histrionicotoxin, which is an amine that causes paralysis. Death from histrionicotoxin results by suffocation through paralysis of the victim s respiratory muscles. (A molecular model of histrionicotoxin is shown above.) Curare, the Amazonian arrow poison that is a mixture of compounds from a woody vine, contains another paralytic neurotoxin, called cf-tubocu-rarine. Histrionicotoxin and d-tubocurarine both block the action of acetylcholine, an important neurotransmitter. Amines like these and others have fascinating roles in biological systems, as we shall see in this chapter while studying the properties, reactivity, and synthesis of amines. 

Excitation and/or emission spectra are measured from a specified area of the specimen using a micro-spectrofluorometer. Such instruments usually have to be assembled by addition of an appropriate light source and monochromators to a microfluorometer. This can be applied either for the identification of unknown fluorophores or to the investigation of the conditions of fluorescence of known fluorophores. The main application to date has been the identification of neurotransmitter amines in situ using formaldehyde-induced fluorescence. 

This is observed following a chemical reaction to convert some non-fluorescent substance, already present in tissue, into a fluorescent substance. The most important example is the demonstration of neurotransmitter amines such as noradrenaline, which can be converted into fluorescent substances by treatment with formaldehyde or glutaraldehyde. 

Fluorescence techniques can be applied to all kinds of material. Because fluorescence microscopy requires more complex and expensive instrumentation than conventional transmitted-light microscopy, fluorescence microscopy is usually reserved for those applications in which its high sensitivity is of importance i.e., to examine substances present in low concentrations. Fluorescence microscopy can also be applied to detect particles below the resolution of a light microscope, and in histochemistry to visualize substances which cannot be seen by conventional microscopy - e.g. neurotransmitter amines. Biological material is commonly stained in some manner with a fluorescent stain. 

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