Catecholamines Dopamine Epinephrine

Histamine, serotonin and the catecholamines (dopamine, epinephrine and norepinephrine) are synthesized from the aromatic amino acids histidine, tryptophan and phenylalanine, respectively. The biosynthesis of catecholamines in adrenal medulla cells and catecholamine-secreting neurons can be simply summarized as follows [the enzyme catalysing the reaction and the key additional reagents are in square brackets] phenylalanine — tyrosine [via liver phenylalanine hydroxylase + tetrahydrobiopterin] —> i.-dopa (l.-dihydroxyphenylalanine) [via tyrosine hydroxylase + tetrahydrobiopterin] —> dopamine (dihydroxyphenylethylamine) [via dopa decarboxylase + pyridoxal phosphate] — norepinephrine (2-hydroxydopamine) [via dopamine [J-hydroxylasc + ascorbate] —> epinephrine (jV-methyl norepinephrine) [via phenylethanolamine jV-methyltransferase + S-adenosylmethionine]. 

These are four monoamines synthesized and seereted within many mammalian tissues, ineluding various regions in the brain, sympathetic nervous system, enlero-chromafhn cells of the digestive tract, and adrenal mednlla. These biogenic amines (indoleamine and catecholamines — dopamine, norepinephrine, and epinephrine) are synthesized within the cell from their precursor amino acids and have been associated with many physiological and behavioral functions in animals and humans. 

The catecholamines dopamine, norepinephrine and epinephrine are neurotransmitters and/or hormones in the periphery and in the CNS. Norepinephrine is a neurotransmitter in the brain as well as in postganglionic, sympathetic neurons. Dopamine, the precursor of norepinephrine, has biological activity in the periphery, most particularly in the kidney, and serves as a neurotransmitter in several important pathways in the CNS. Epinephrine, formed by the N-methylation of norepinephrine, is a hormone released from the adrenal gland, and it stimulates catecholamine receptors in a variety of organs. Small amounts of epinephrine are also found in the CNS, particularly in the brainstem. 

In contrast, much is known about the catabolism of catecholamines. Adrenaline (epinephrine) released into the plasma to act as a classical hormone and noradrenaline (norepinephrine) from the parasympathetic nerves are substrates for two important enzymes monoamine oxidase (MAO) found in the mitochondria of sympathetic neurones and the more widely distributed catechol-O-methyl transferase (COMT). Noradrenaline (norepinephrine) undergoes re-uptake from the synaptic cleft by high-affrnity transporters and once within the neurone may be stored within vesicles for reuse or subjected to oxidative decarboxylation by MAO. Dopamine and serotonin are also substrates for MAO and are therefore catabolized in a similar fashion to adrenaline (epinephrine) and noradrenaline (norepinephrine), the final products being homo-vanillic acid (HVA) and 5-hydroxyindoleacetic acid (5HIAA) respectively. 

Similarly, the effects of SNA on the catecholamine (norepinephrine, epinephrine, dopamine) systems have been widely studied, but the results are far from clear. SNA has been reported to Increase rat brain tyrosine and to decrease rat brain norepinephrine (NE) and to Increase dopamine (DA) slightly.Again, conflicting results are available.31 Apparently, changes In these biogenic... 

Methylation S- Adenosylmethionine Transmethylases (cytosol) Catecholamines, phenols, amines Dopamine, epinephrine, pyridine, histamine, thiouracil... 

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. 

Other important nitrogen-containing compounds made from amino acids include the catecholamines (dopamine, norepinephrine, and epinephrine), which are synthesized from tyrosine creatine, which is synthesized from arginine and glycine histamine, which is synthesized from histidine and serotonin, which is synthesized from tryptophan. 

Catecholamine A group of chemically similar compounds that are important in the modulation of cardiovascular activity and many other physiologic functions. Common catecholamines include epinephrine, norepinephrine, and dopamine. 

The catecholamines - dopamine, norepinephrine, and epinephrine are successively derived from tyrosine. S m-thesis occurs in the nerve terminals and in the adrenal gland. Tyrosine hydroxylase catalyzes the first step (Figure 10.2a) and is the major site of regulation (inhibition by dopamine and noradrenaline, activation by cAMP). This step gives rise to 3,4-dihydroxyphenylalanine (L-DOPA), which in turn is a substrate for L-aromatic acid decarboxylase. De-... 

In intensive care settings, sympathomimetic catecholamines [e.g., dobutamine, dopamine, epinephrine (adrenaline), isoprenaline (isoproterenol), norepinephrine (noradrenaline, and levarterenol] are often administered via continuous infusion. In clinical practice, reservoirs and administration sets of these drugs are routinely changed every 12 or 24 hours. As the pharmacological efficacy of catecholamines is directly related to their intact phenolic groups, their stability over these dosing periods is questionable. 

NE is synthesized by tyrosine hydroxylation (meta ring position) followed by decarboxylation and side chain p carbon hydroxylation. The synthesis of this catecholamine is regulated by tyrosine hydroxylase. Tyrosine hydroxylation is also a key step in the synthesis of two other important catecholamines, dopamine and epinephrine. NE is packaged via active transport into synaptic (or chromaffin) vesicles prior to release by neuronal depolarization. The effects of NE are mediated by adrenergic receptors (a or P) which are G protein coupled resulting in either increases or decreases in smooth muscle tone as well as increases in cardiac rate and contractility. These effects arise out of receptor mediated increases in intracellular Ca and activation or inhibition of various protein kinases. The effects of NE are terminated essentially as a result of its active transport into the presynaptic nerve ending via an energy and Na" dependent process which utilizes the norepinephrine transporter (NET). Ultimately, NE and other catecholamines are metabolized by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). 

Figure 16-2 Biosynthesis of the catecholamines dopamine, o epinephrine, and epinephrine.

The three naturally occurring catecholamines dopamine, NE, and epinephrine are used as therapeutic agents. 

The catecholamines (dopamine, norepinephrine, and epinephrine) are derived from dopa in a series of reactions (see Figure 7-12). -Decarboxylation of dopa forms the neurotransmitter dopamine. -Hydroxylation of dopamine on its aliphatic chain by an enzyme that... 

THE AROMATIC FAMILY The aromatic family of amino acids includes phenylalanine, tyrosine, and tryptophan. Of these, only tyrosine is considered to be nonessential in mammals. Either phenylalanine or tyrosine is required for the synthesis of dopamine, epinephrine, and norepinephrine, an important class of biologically potent molecules referred to as the catecholamines (Special Interest Box 14.2). Tryptophan is a precursor in the synthesis of NAD+, NADP+, and the neurotransmitter serotonin. 

The catecholamines (dopamine, norepinephrine, and epinephrine) are derivatives of tyrosine. Dopamine (D) and norepinephrine (NE) are used in the brain as excitatory neurotransmitters. Outside the central nervous system, NE and epinephrine (E) are released primarily from the adrenal medulla, as well as the peripheral nervous system. Because both NE and E regulate aspects of metabolism, they are often considered hormones. 

The naturally occurring catecholamines dopamine (1), norepinephrine (2), and epinephrine(3) (Figure 1) play key roles in neurotransmission, metabolism, and in the control of various physiological processes. For example, norepinephrine is the primary neurotransmitter in the sympathetic nervous system and also functions as a neurotransmitter in the central nervous system. Epinephrine, elaborated by the adrenal gland, has potent effects on the heart, vascular and other smooth muscles. Dopamine is an important neurotransmitter in the central nervous system, and has important peripheral effects in such organs as the kidney and heart. The importance of these effects has made the search for drugs that can mimic, inhibit, or otherwise modulate the effects of these catecholamines an important area of medicinal chemistry. 

Figure 1 Naturally occurring catecholamines Dopamine (1), norepinephrine (2), and epinephrine (3).

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. 

The term catecholamine comes from the aromatic dialcohol, catechol. The most common catecholamines are epinephrine, norepinephrine, dopamine, and dihydroxyphenylalanine (L-Dopa). 

Dopamine is a catecholamine derived from tyrosine. Other catecholamines include epinephrine and norepinephrine. The biosynthetic pathway from tyrosine to dopamine, and the other catecholamines is shown in Figure 21.32. 

Catecholamines (dopamine, deoxyepinepherine, epinephrine, isoproterenol, norepinephrine, seroto-nine)... 

CATECHOLAMINES The brain contains separate neuronal systems that utilize three different catecholamines—dopamine (DA), norepinephrine (NE), and epinephrine (Epi). Each system is anatomically distinct and serves separate, but similar, functional roles within its field of innervation. 

In patients suspected of having a neoplasm of the adrenal medulla that is secreting excessive quantities of epinephrine or norepinephrine (a pheochromocytoma), either the catecholamines themselves (epinephrine, norepinephrine, and dopamine) or their metabolites (the metanephrines and vanillylmandelic acid, VMA) may be measured in a 24-hour urine collection, or the level of catecholamines in the blood may be measured. A patient who has consistently elevated levels in the blood or urine should be considered to have a pheochromocytoma, particularly if the patient has signs and symptoms of catecholamine excess, such as excessive sweating, palpitations, tremulousness, and hypertension. 

A number of methyltransferases are able to methylate small molecules either on a phenolic, an amino or a thiol group. The major enzyme responsible for 0-methylations is catechol 0-methyltransferase (COMT), a cytosolic enzyme that also exists in membrane-bound form. This enzyme catalyses the 0-methylation of catecholamines (dopamine, norepinephrine, epinephrine), L-dopa and related catechol drugs. 

M AOB by blocking entry into neurons of the catecholamines, dopamine, norepinephrine, and epinephrine. 

Monitor the ECG for at least 4-6 hours, and treat arrhythmias (pp 10-15) if they occur. Avoid the use of catecholamines (eg, epinephrine, dopamine), which may precipitate cardiac arrhythmias. Tachyarrh hmias caused by myocardial sensitization may be treated with esmolol (see p 443),... 

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