Amines as neurotransmitters

Several naturally occurring amines mediate the transmission of nerve impulses and are referred to as neurotransmitters Two examples are epinephrine... 

Biogenic amines. A general term usually used to describe endogenous amine-containing compounds such as dopamine, 5-hydroxy-tryptamine, and norepinephrine that function as neurotransmitters. 

Ubiquitous mitochondrial monoamine oxidase [monoamine oxygen oxidoreductase (deaminating) (flavin-containing) EC 1.4.3.4 MAO] exists in two forms, namely type A and type B [ monoamine oxidase (MAO) A and B]. They are responsible for oxidative deamination of primary, secondary, and tertiary amines, including neurotransmitters, adrenaline, noradrenaline, dopamine (DA), and serotonin and vasoactive amines, such as tyramine and phenylethylamine. Their nonselec-tive and selective inhibitors ( selective MAO-A and -B inhibitors) are employed for the treatment of depressive illness and Parkinson s disease (PD). 

Biogenic amines are decarboxylated derivatives of tyrosine and tryptophan that are found in animals from simple invertebrates to mammals. These compounds are found in neural tissue, where they function as neurotransmitters, and in non-neural tissues, where they have a variety of functions. The enzymes involved in biogenic amine synthesis and many receptors for these compounds have been isolated from both invertebrate and vertebrate sources. In all cases, the individual proteins that effect biogenic amine metabolism and function show striking similarity between species, indicating that these are ancient and well-conserved pathways. 

Histamine, serotonin, melatonin, and the catecholamines dopa, dopamine, norepinephrine, and epinephrine are known as "biogenic amines."They are produced from amino acids by decarboxylation and usually act not only as hormones, but also as neurotransmitters. 

Dopamine, norepinephrine, and epinephrine (adrenalin) are biologically active amines that are collectively termed catecholamines. Dopamine and norepinephrine function as neurotransmitters in the brain and the autonomic nervous system. Norepinephrine and epinephrine are also synthesized in the adrenal medulla. 

The excretion of amines is unusual in animals. Amines are highly toxic and one method employed by vertebrates to detoxify them is via monoamine oxidase, an enzyme which has been detected in H. diminuta (569). Amines can arise from the decarboxylation of the appropriate amino acid, e.g. glycine and alanine can give rise to methylamine and ethylamine, respectively. Another possible source of amines may be the reduction of azo or nitro compounds (39) and azo- and nitro-reductase activity has been reported from M. expansa (180, 181). Furthermore, the physiologically active amines octopamine, dopamine, adrenalin and serotonin (5-hydroxytryptamine) have been demonstrated in cestodes (283, 296, 435, 681, 682, 758, 859), where they probably function predominantly as neurotransmitters (see Chapter 2). 

Neurotransmitters derive from amino adds most of them are amines that become protonated under physiological conditions. Since alkaloids also derive from amino acids (often the same ones as neurotransmitters) it is no surprise that several alkaloids have structural similarities to neurotransmitters. They can be considered as neurotransmitter analogs (Figure 1.5a-c). 

GC-MS has found wide application in studies of monoamines in both animal models and in human neuropharmacology [452]. Interest has centred on the use of selected ion monitoring in the determination of trace amounts of the amines, their metabolites and related substances with a possible function as neurotransmitters. The SIM approach complements established assay methods such as gas chromatography with electron capture detection (ECD), fluorimetry or enzymic assay. A check on specificity is afforded and in many cases enhancement in sensitivity and precision of measurement can be obtained. Method development, principally relating to estimation of central amine turnover, is noted in this Section and an outline of work on human depression serves to illustrate the potential of GC-MS to the study of CNS dysfunction. 

Amine hormones and some agents of the second type have counterparts in the nervous system that function as neurotransmitters. 

MAOs are mitochondrial flavoproteins containing one covalently bound FAD cofactor. Two isozymes, termed as MAO-A and MAO-B, are known for the MAO enzyme family. They catalyze the oxidative deamination of structurally diverse amines including neurotransmitters dopamine, norepinephrine, serotonin, tyramine, and 2-phenylethylamine, and some drugs and xenobiotics that contain cyclic and acyclic alkylamine functional groups [67, 68]. The MAO reaction cycle involves two half reactions, as shown in equations 1.3a and 1.3c ... 

From the studies so far described it seemed that LSD was almost unique amongst centrally acting compounds in the potency of its effects on the caeruloplasmin-catalysed oxidation of NA and 5-HT, and this has led to the suggestion that this enzyme, or one with similar properties, may be directly involved in the mode of action of LSD. It is known that the Km values for NA and 5-HT are almost identical, suggesting that caeruloplasmin or an enzyme with similar properties could exercise a very sensitive control over the relative concentrations of these two amines (and probably also dopamine) in those parts of the brain where they act as neurotransmitters. If, as seems likely, the maintenance of a balance between NA, dopamine and 5-HT is essential to normal mental function, then LSD could produce its central effects by disturbing the balance between these biogenic amines as a result of its interaction with caeruloplasmin or a similar enzyme moreover, since LSD affects the... 

Among the most important neurotransmitters are acetylcholine (ACh), amino acids and their derivatives, and certain polypeptides known as neuropeptides. In fact, the mammalian nervous system is said to employ over 30 different substances as neurotransmitters. For the record, among the amino acids and their derivatives (called biogenic amines) are many that are also hormonally active in the bloodstream, and include the catecholamines dopamine, norepinephrine, and epinephrine, as derived sequentially from tyrosine, whereas y-aminobutyric acid (GABA), histamine, and serotonin are derived from glutamate, histidine, and tryptophan, respectively. The subject interfaces with the biochemical aspects of psychology, which may also be referred to as the mind-body connection, or psychosomatics. 

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