Amines epinephrine

Compounds stmcturaHy related to the endogenous sympathomimetic amines epinephrine and norepinephrine have classically been employed as appetite suppressants. These agents, of which amphetamine [300-62-9], is the prototypical example, generally retain the phenethyl amine, but lack... 

Hormones Some lipophilic hormones (e.g. the steroid hormones, thyroxine, retinoic acid and vitamin D) diffuse across the plasma membrane and interact with intracellular receptors in the cytosol or nucleus. Other lipophilic hormones (e.g. the prostaglandins) and hydrophilic hormones (e.g. the peptide hormones insulin and glucagon and the biogenic amines epinephrine and histamine) bind to receptor proteins in the plasma membrane. 

The enzymes, amino acid decarboxylases are pyridoxal phosphate- dependent enzymes. Pyridoxal phosphate forms a Schiff s base with e amino acid so as to stabilise the a-carbanion formed by the cleavage of bond between carboxyl and a-carbon atom. The physiologically active amines epinephrine, nor-epinephrine, dopamine, serotonin, y-amino butyrate and histamine are formed through decarboxylation of the corresponding precursor amino acids... 

The enhancement of ozone injury in animals by activity during exposure to ozone has been the most striking demonstration of all. The lethal outcome of otherwise noninjurious concentrations of ozone results undoubtedly from a multiplicity of factors in addition to that of the more obvious reactions associated with activity such as increased respiration and circulation rates. Hormonal releases, for example, in the form of catechol amines, epinephrine, and norepinephrine, as well as in certain adrenocorticosteroids (compounds B and F) have been reported in tumbled rats (9), a condition not completely unrelated to that in cage-activated rats, especially during the terminal phases on the exposure. How much of a role these hormones play in these experiments, however, still remains to be determined. 

Cardiotoxicity of primary amines (epinephrine, norepinephrine, isoproterenol) was noted earlier, and has been recognized for nearly 100 years. The vascular toxicity of these and related compounds has also recently been recognized. The effects seem to focus on medial cells of the artery wall, rather than on adventitial or endothelial cells. Early changes include loss of medial cells, mineralization, and loss of elastic fibers. Later there is a compensatory proliferation of intimal cells. The vascular toxicity of two related compounds is particularly striking. One of these compounds, allylamine, will be discussed near the end of this chapter. The second is )S-aminoproprionitrile ()S-APN), which is the active agent in the toxic sweet pea, Lathyrus odoratus. Consumption of flour derived from this plant results in lathyrism, a condition often seen in children and young... 

Compounds structurally related to the endogenous sympathomimetic amines epinephrine and norepinephrine have classically been employed as appetite suppressants. These agents, of which amphetamine [300-62-9], C9H13N, is the prototypical example, generally retain the phenethylamine, but lack the catechol moiety present in the natural substances. As a consequence, they are well absorbed after oral administration and readily distribute into the central nervous system where they exert their anorectic effects at hypothalamic appetite control centers. A component of their efficacy in promoting weight... 

Several amines are known to have specific biological functions. Some obvious examples are histamine and serotonin (5-hydroxytryptamine), which are produced by decarboxylation of the corresponding amino acids. The secondary amine, epinephrine, is formed in an incompletely elucidated pathway from phenylalanine. In addition to these compounds with potent pharmacological activity, other amines seem to play vital... 

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

Fig. 2. Chemical stmcture of the endogenous catecholamines, epinephrine (8), and norepinephrine (7), and several synthetic phenethano1 amines that alter...

Epinephrine itself does find some use in clinical medicine. The drug is used in order to increase blood pressure in cases of circulatory collapse, and to relax the bronchial muscle in acute asthma and in anaphylactic reactions. These activities follow directly from the agent s physiologic role. The biogenetic precursor of epinephrine, norepinephrine, has activity in its own right as a mediator of sympathetic nerve action. (An apocryphal story has it that the term nor is derived from a label seen on a bottle of a key primary amine in a laboratory in Germany N ohne... 

Epinephrine (adrenaline). A biogenic amine released from the adrenal medulla, particularly in moments of stress. 

The phenyl ethanol amine derivatives epinephrine (U and norepinephrine ( ) are intimately associated with the sympathetic nervous system. These two neurotransmitter hor-... 

Catecholamines are biogenic amines with a catechol (o-dihydroxy-benzol) structure. They are synthesized in nerve endings from tyrosine and include dopamine, noradrenaline (norepinephrine) and adrenaline (epinephrine). 

The TCAs, such as amitriptyline (Elavil) and dox-epin (Sinequan), inhibit reuptake of norepinephrine or serotonin at the presynaptic neuron. Drug classified as MAOIs inhibit the activity of monoamine oxidase a complex enzyme system that is responsible for breaking down amines. This results in an increase in endogenous epinephrine, norepinephrine and serotonin in the nervous system. An increase in these neurohormones results in stimulation of the CNS. The action of the SSRIs is linked to their inhibition of CNS neuronal uptake of serotonin (a CNS neurotransmitter). The increase in serotonin levels is thought to act as a stimulant to reverse depression. 

Neural cells convert tyrosine to epinephrine and norepinephrine (Figure 31—5). While dopa is also an intermediate in the formation of melanin, different enzymes hydroxylate tyrosine in melanocytes. Dopa decarboxylase, a pyridoxai phosphate-dependent enzyme, forms dopamine. Subsequent hydroxylation by dopamine P-oxidase then forms norepinephrine. In the adrenal medulla, phenylethanolamine-A -methyltransferase uti-hzes S-adenosyhnethionine to methylate the primary amine of norepinephrine, forming epinephrine (Figure 31-5). Tyrosine is also a precursor of triiodothyronine and thyroxine (Chapter 42). 

Three amines—dopamine, norepinephrine, and epinephrine—are synthesized from tyrosine in the chromaffin cells of the adrenal medulla. The major product of the adrenal medulla is epinephrine. This compound constimtes about 80% of the catecholamines in the medulla, and it is not made in extramedullary tissue. In contrast, most of the norepinephrine present in organs innervated by sympathetic nerves is made in situ (about 80% of the total), and most of the rest is made in other nerve endings and reaches the target sites via the circu-... 

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. 

Figure 1. Biosynthetic pathways for biogenic amines. In Drosophila and vertebrates decarboxylation of DOPA and 5-hydroxy-tryptophan is catalyzed by the same enzyme, DDC. In vertebrates this enzyme is called amino acid decarboxylase (AADC). Only vertebrates further metabolize dopamine to norepinephrine and epinephrine. TH, tryosine hydroxylase DDC, DOPA decarboxylase DBH, dopamine b-hydroxylase PNMT, phenylethanolamine N-methyltransferase. Tryp-OH tryptophan hydroxylase.

In the vertebrate CNS monoamines have been associated with a number of physiological functions (reviewed in Kandel et al., 1991). Serotonin has functions associated with mood, pain, sleep, learning, and memory. Dopamine has functions associated with schizophrenia, Parkinson s disease, and cocaine addiction. In vertebrates, dopamine is further metabolized into two additional neurotransmitters, norepinephrine and epinephrine. Norepinephrine increases the excitability of cells in response to sudden sensory input such as fear. Epinephrine has been identified in specific neurons of the brain, but the function of these cells is unknown. In addition, AADC has also been found in a class of neurons that do not have any of the four neurotransmitters discussed above (Jaeger et al., 1983). These neurons may use one of the trace amines, tyramine, tryptamine, or phenylethylamine, as a neurotransmitter. 

Figure 3 Putative model for the mechanism by which biogenic amines stimulate CE secretion across the rabbit corneal epithelium. Epn = epinephrine Nep = norepinephrine Tim = Timolol Ser = serotonin Msg = methysergide Dop = dopamine Hal = haloperi-dol (E = (E-adrenoceptor AC = adenylate cyclase. The scheme is consistent with the observation that epithelial responsiveness to serotonin and dopamine can be blocked by their receptor antagonists haloperidol and methysergide, respectively, and by both timolol treatment and sympathectomy. The probable source of serotonin or dopamine is the sympathetic fibers that innervate the cornea. (From Ref. 284.)...

Femtomol levels of detection limits were also achieved in the determination of stimulant amines with the benzofurazan derivative 4-(Af,Af-dimethylaminosul-phonyl)-7-fluoro-2,l,3-benzoxadizole (DBD-F) [73], DBD-F was successfully applied to the PO-CL detection of amino acids and epinephrine [74] and a P-blocker, metoprolol [75], 4-(Af,Af-Dimethylaminosulphonyl)-7-hydrazino-2,l,3-benzoxadizole (DBD-H) has also been used for PO-CL determination of a neuronal cell protective compound, propentofylline. The method was applied for the first time to determine propentofylline concentration in the dialysate obtained from the rat hippocampus [85],... 

In cells that synthesize epinephrine, the final step in the pathway is catalyzed by the enzyme phenylethanolamine /V-methyltransferase. This enzyme is found in a small group of neurons in the brainstem that use epinephrine as their neurotransmitter and in the adrenal medullary cells, for which epinephrine is the primary hormone secreted. Phenylethanolamine N-methyltransferase (PNMT) transfers a methyl group from S-adenosylmethionine to the nitrogen of norepinephrine, forming a secondary amine [5]. The coding sequence of bovine PNMT is contained in a... 

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