Adrenaline and Noradrenaline

Halogenated hydrocarbons depress cardiac contractility, decrease heart rate, and inhibit conductivity in the cardiac conducting system. The cardiac-toxicity of these compounds is related to the number of halogen atoms it increases first as the number of halogen atoms increases, but decreases after achieving the maximum toxicity when four halogen atoms are present. Some of these compounds, e.g., chloroform, carbon tetrachloride, and trichloroethylene, sensitize the heart to catecholamines (adrenaline and noradrenaline) and thus increase the risk of cardiac arrhythmia. 

Together with dopamine, adrenaline and noradrenaline belong to the endogenous catecholamines that are synthesized from the precursor amino acid tyrosine (Fig. 1). In the first biosynthetic step, tyrosine hydroxylase generates l-DOPA which is further converted to dopamine by the aromatic L-amino acid decarboxylase ( Dopa decarboxylase). Dopamine is transported from the cytosol into synaptic vesicles by a vesicular monoamine transporter. In sympathetic nerves, vesicular dopamine (3-hydroxylase generates the neurotransmitter noradrenaline. In chromaffin cells of the adrenal medulla, approximately 80% of the noradrenaline is further converted into adrenaline by the enzyme phenylethanolamine-A-methyltransferase. 

The biological actions of adrenaline and noradrenaline are mediated via nine different G-protein-coupled receptors, which are located in the plasma membrane of neuronal and nonneuronal target cells. These recqrtors are divided into two different groups, a-adrenergic receptors and P-adrenergic recqrtors (see P-adrenergic system). 

Sympatholytic drugs are a group of drugs, which decrease the activity of the sympathetic nervous system, mainly by blocking the action of adrenaline and noradrenaline at adrenoceptors. 

Ephedrine enhances the release of the hormone norepinephrine in the body, and also binds to the same receptors as that hormone, causing excess calories to be converted to heat instead of being stored as fat. It also raises blood pressure. Epinephrine and norepinephrine are also known as adrenaline and noradrenaline. Ephedrine thus acts to stimulate an adrenaline rush. 

There is 5-hydroxytryptamine in weever fish venom besides protein. It is believed that local pain is attributed to the presence of 5-hydroxytryptamine (27). Other small compounds such as histamine, adrenaline, and noradrenaline are also present in the weever fish (28). 

Adrenal gland A triangle-shaped organ positioned at the top of the kidney which functions as a double endocrine gland . The larger outer adrenal cortex secretes three classes of steroid hormones glucocorticoids (e.g., cortisol), minerlocorticoids (aldosterone) and small amounts of sex steroids (e.g., testosterone). The inner adrenal medulla secretes catecholamines (e.g., adrenaline and noradrenaline). 

It has been suggested by Augustinsson1 that adrenaline and noradrenaline can protect cholinesterase. However, adrenaline cannot protect below a concentration of 0-1 mM, and it is therefore unlikely that mobilization of adrenaline in vivo could influence the inhibition of cholinesterase. 

The maximum level of HMMA in the urine occurred 72 hours after exposure, which coincides with the time period for maximum urine catecholamine levels. There was a direct relationship between blood cholinesterase inhibition and catecholamine (adrenaline and noradrenaline) levels in the urine and blood (Brzezinski and Ludwicki 1973). Maximum inhibition of cholinesterase activity and maximum plasma catecholamine occurred during the first I-2 hours after exposure. However, catecholamine levels returned to normal more rapidly than cholinesterase activity. It was proposed that high levels of acetylcholine, which are normally associated with cholinesterase activity inhibition, caused a release of catecholamines from the stores in the adrenals. 

Brzezinski J. 1973. The effect of atropine on the levels of adrenaline and noradrenaline changed by acute poisoning with Di-Syston in rats. Pol J Pharmacol Pharm 25 611-615. 

Studies of the oxidation products of catecholamines (i.e., seretonin, dopamine, dopa, adrenaline, and noradrenaline) have indicated that protein oxidation by quinones may lead to apoptosis. Oxidation results in formation of orrto-quinones, which contribute to cytotoxicity and have been suggested... 

Before we leave adrenaline and noradrenaline, I want to take advantage of the opportunity to develop the mechanism of action of some of our most important and widely employed drugs in human medicine. 

Back in 1913, adrenaline was found to cause either constriction or relaxation of blood vessels, depending on the anatomical site. Scientists correctly concluded that there must be two classes of adrenergic receptors. These are termed alpha and beta adrenergic receptors. When adrenaline hits the alpha-type receptor, blood vessel constriction results at the beta-type receptor, blood vessel relaxation results. Thus, adrenaline and noradrenaline are nonspecific agonists (activators) at adrenergic receptors. 

Adrenergic receptor one of several classes of membrane-localized receptors that recognize adrenaline and noradrenaline as agonists. 

Stress and stress hormones Anxiety or stress can increase energy expenditure, although the effect is small. It is caused by increased sympathetic activity and hence increased levels of the stress hormones adrenaline and noradrenaline. Injection of these hormones increases oxygen consumption, as does caffeine, which... 

The recommended International Non-proprietary Name (rINN) is used throughout the book, except when the terms used are adrenaline and noradrenaline. For further reference, see the British National Formulary. 

Cortical hormones include glucocorticoids (cortisol/corticosterone) and mineralocorticoids (aldosterone) medullar hormones are adrenaline and noradrenaline Pancreas Regulates glucose in blood via production of the hormones glucagon and insulin... 

L3. Levi, L., The urinary output of adrenalin and noradrenalin during pleasant and unpleasant emotional states. A preliminary report. Psychasom. Med. 27, 80-85 (1965). 

Sundin, T., The effect of body posture on the urinary excretion of adrenaline and noradrenaline. Acta Med. Scand., Suppl. 336, 1-59 (1958). 

The adrenergic receptors (or adrenoceptors) are a class of G-protein coupled receptors, which are the targets of catecholamines. Adrenergic receptors specifically bind their endogenous ligands, the catecholamines, epinephrine, and norepinephrine (also called adrenaline and noradrenaline), and are activated by these. 

The most frequently used antiadrenergic drugs for hypertension therapy are the fi-adrenoblockers. Despite the fact that they have been used for many years, their mechanism of action is not completely understood. Only one thing is clear—they are competitive antagonists of adrenaline and noradrenaline on cardiac j3-adrenergic receptors. 

Adrenergic receptors are located throughout the body on neuronal and nonneuronal cells where they mediate a diverse range of responses to the endogenous catecholamines adrenaline and noradrenaline. To date, nine... 

Adrenaline and noradrenaline induee a wide variety of biological responses, including ... 

Figure 1.8. Structure of adrenaline and noradrenaline. Both are catecholamines (amide-containing...

Adrenaline and noradrenaline are unstable in aqueous solution where they are subjected to spontaneous oxidation. In vivo this mechanism is only relevant under pathophysiological conditions of an catecholamine excess, since two enzymes, the catechol-O-methyltransferase (COMT) and the monoamineoxidase (MAO), inactivate physiological amounts of the transmitters. There are at least two subtypes of the enzyme MAO, A and B, which can be inhibited selectively for therapeutic purposes, for example by moclobemide and selegiline. 

Qualitatively the effects of adrenaline and noradrenaline at the heart is similar, although noradrenaline is somewhat less effective. The... 

Adrenaline and noradrenaline reduce the peristaltic movements and the frequency of the intestinal smooth muscle both by a- and /3-adrenoceptor stimulation. The stimulation of 2-adrenoceptors at presynaptic neurons in the intestinal plexus reduces the release of activating transmitters, such as acetylcholine. 

Dopamine is an intermediate product in the biosynthesis of noradrenaline. Furthermore it is an active transmitter by itself in basal ganglia (caudate nucleus), the nucleus accumbens, the olfactory tubercle, the central nucleus of the amygdala, the median eminence and some areas in the frontal cortex. It is functionally important, for example in the extra-pyramidal system and the central regulation of emesis. In the periphery specific dopamine receptors (Di-receptors) can be found in the upper gastrointestinal tract, in which a reduction of motility is mediated, and on vascular smooth muscle cells of splanchnic and renal arteries. Beside its effect on specific D-receptors, dopamine activates, at higher concentrations, a- and -adrenoceptors as well. Since its clinical profile is different from adrenaline and noradrenaline there are particular indications for dopamine, like situations of circulatory shock with a reduced kidney perfusion. Dopamine can dose-dependently induce nausea, vomiting, tachyarrhythmia and peripheral vasoconstriction. Dopamine can worsen cardiac ischaemia. 

Sympathomimetics are drugs which resemble the phenylalkylamine structure of the catecholamines and induce similar effects as adrenaline and noradrenaline. According to their molecular mechanism there are direct- and indirect-acting sympathomimetic drugs, the latter of which release noradrenaline from and/or inhibit its re-uptake into the presynaptic sympathetic axon. 

The analyte is loaded onto the gel in a buffer at ca pH 7.0 and the complex formed can then be broken down using a mildly acidic eluent such as 0.1 M acetic acid. This type of extraction has been applied to the determination of dopamine, adrenaline and noradrenaline in plasma and to the determination of the extent of reaction of glucose with serum albumin as a measure of glucose fluctuations with time in diabetics. 

The L-isomers are the naturally occurring forms of epinephrine and norepinephrine and possess considerably greater pharmacological effects than do the D-isomers. Throughout most of the world, epinephrine and norepinephrine are known as adrenaline and noradrenaline, respectively. 

Pharmacological Action of Sympathomimetics (Particularly adrenaline and noradrenaline)... 

Blood vessels Adrenaline and noradrenaline constrict the blood vessels of skin and mucous membranes. Constriction predominates in cutaneous and mucous membranes which occur through both and receptors. Adrenaline also dilates the... 

Restlessness, anxiety, tremor, headache. Both adrenaline and noradrenaline cause sudden increase in blood pressure, precipitating sub-arachnoid haemorrhage and occasionally hemiplegia, and ventricular arrhythmias. May produce anginal pain in patients with ischemic heart disease. 

These are the agents, which block the action of adrenaline and noradrenaline. They block either alpha or beta or both adrenergic receptors. They are classified as in table 3.3.1 and 3.3.2. 

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