Adrenaline mechanism

Molar absorptivity. 502 Molecular ion (M+), 410 Molecular mechanics. 130 Molecular model, dopamine, 930 acetaminophen, 29 acetylene, 18 adenine, 67 adrenaline, 323 alanine, 28, 1016 alanylserine, 1028 rr helix, 1039 p-aminobenzoic acid, 25 anti periplanar geometry, 387 a recoline, 79 aspartame, 29 aspirin. 17 ball-and-stick, 61 /3-pleated sheet, 1039 p-bromoacetophenone, 449 bromocyclohexane, 121 butane, 80... 

Several mechanisms serve to terminate the biological actions of noradrenaline and adrenaline. From the... 

Caffeine binds to adenosine receptors in the brain, preventing adenosine from inducing sleep or opening blood vessels. Caffeine also increases levels of dopamine, the neurotransmitter associated with pleasure. This is the chemical mechanism for addiction. The response to adenosine competition causes increased adrenaline flow. 

Patients with chronic idiopathic urticaria, who develop cutaneous reactions in response to aspirin, display certain similarities in eicosanoid profile with AIA. The mechanism of the reactions is often related to COX-1 inhibition [18]. Therefore, aspirin and all drugs that inhibit COX-1 should be avoided in patients who already have had cutaneous reactions to NSAID. Coxibs are usually well tolerated, although occasional adverse reactions have been reported [19, 20]. For treatment of the reactions, antihistamines are usually sufficient, but in more severe cases adrenaline and corticosteroids may be warranted. 

Adrenalin, chloroacetyl chloride in production of, 7 142 P-Adrenergic agonists as animal growth regulators, 73 14-17 genotype, gender, and nutritional interactions related to, 73 16 mechanism of action of, 73 17 Adrenergic neuronal blockers,... 

Inhalation of certain hydrocarbons, including some anesthetics, can make the mammalian heart abnormally sensitive to epinephrine, resulting in ventricular arrhythmias, which in some cases can lead to sudden death (Reinhardt et al. 1971). The mechanism of action of cardiac sensitization is not completely understood but appears to involve a disturbance in the normal conduction of the electrical impulse through the heart, probably by producing a local disturbance in the electrical potential across cell membranes. The hydrocarbons themselves do not produce arrhythmia the arrhythmia is the result of the potentiation of endogenous epinephrine (adrenalin) by the hydrocarbon. 

Although some steroids have been reported to reduce the toxic effects of some insecticides, the steroid ethylestrenol decreased the rate of recovery of depressed cholinesterase activity in disulfoton- pretreated rats (Robinson et al. 1978). The exact mechanism of this interaction was not determined. Ethylestrenol alone caused a small decrease in cholinesterase activity, and, therefore, resulted in an additive effect. Rats excreted less adrenaline and more noradrenaline when given simultaneous treatments of atropine and disulfoton compared with rats given disulfoton alone (Brzezinski 1973). The mechanism of action of disulfoton on catecholamine levels may depend on acetylcholine accumulation. In the presence of atropine, the acetylcholine effect on these receptors increases the ability of atropine to liberate catecholamines. 

Reversible phosphorylation is the main control mechanism of liver phosphorylase allosteric effects being much less pronounced. This is in contrast with muscle phosphorylase, which is also controlled by phosphorylation, stimulated by an adrenaline-... 

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. 

Figure 12.6 Effector mechanism activation of adenyi cyclase via a G-protein. The activation of adenyi cyclase, which resides on the cytosolic side of the cell membrane, is mediated through the membrane-bound G-protein system (see below for biochemistry and role of the G-protein). An example is adrenaline binding to the p-receptor.

Figure 12.5 Effector mechanism activation of a membrane-bound phospholipase. An example is activation of a membrane-bound phospholipase which hydrolyses phosphatidylinositol bisphosphate (PIP2) and results in the formation of the two messengers, inositol trisphosphate (IP3) and diacylglycerol (DAG). Messenger IP3 binds to a receptor on the endoplasmic reticulum that results in release of Ca ions into the cytosol. DAG, which remains within the membrane, activates protein kinase-C at the membrane surface. When the kinase leaves the membrane, it is unclear how it remains active or loss of activity is prevented, so that it can phosphorylate proteins in the cytosol or even the nucleus. An example is adrenaline binding to the a-receptor in the liver, in which Ca ions stimulate glycogenolysis.

It is believed that the mechanism of action of amphetamines lies in their ability to release epinephrine (adrenaline) and dopamine from presynaptic nerve endings, which stimulate the corresponding receptors in the CNS. It is also possible that they reduce neuronal uptake of amines as well as inhibit their degradation by monoaminoxidase (MAO). Characteristic of this series of compounds is the effect on the respiratory center, on the satiation center located in the hypothalamus, which leads to suppression of feelings of hunger, thus allowing analog of the examined compounds to be used as anorectics. 

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. 

In the sympathetic part of the peripheral autonomic nervous system the simation is less complicated since only the sympathetically innervated visceral organs have receptors sensitive to the transmitter of the postganglionic sympathetic neuron noradrenaline. However, the noradrenaline sensitive receptors, which all belong to the G-protein coupled receptor superfamily, can be subdivided in at least three subtypes ai-, a - and jSi-adrenoceptors. These receptors are to a similar extent sensitive to adrenaline, a humoral transmitter which is released under sympathetic control from the adrenal medulla. Adrenaline, in contrast to noradrenaline has affinity to a forth type, the /32-adrenoceptor. In general drug interacting with the autonomous nervous system can be subdivided according to their mechanism of action. 

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. 

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. 

While the inhibition of noradrenaline re-uptake exerts predominantly an a-adrenergic effect, a selective jS-adrenergic effect can not be obtained by such an indirect mechanism. All selective /3-sympathomi-metics activate the receptors, P -, P2- or both sub-types, directly. The first pure jS-sympathomimetic in clinical use was isoproterenol which is structurally identical to adrenaline except the methyl-moiety at the N-position in the side-chain is replaced by an isopropyl-group. All effects produced by isoproterenol are due to either P -or 62-adrenoceptor stimulation tachycardia, increased stroke volume, decreased vascular resistance, broncho dilatation and, in pregnancy, uterus relaxation. The metabolic effects of isoproterenol are less pronounced than those of adrenaline. 

The ion-exchange mechanism of exfracfion does nof occur only for amino acids. We observed if also for cafecholamines [26]. These compounds are efficiently extracted into ILs in the cationic form, af pH 1-8. Af fhese pH, the primary (dopamine) or secondary (adrenaline and dobutamine) amino groups are protonated (catecholamines are oxidized in alkaline solutions at pH > 8). By analogy with amino acids, extraction may be described by the cation-exchange reaction ... 

In other cells, i.e. in rat submandibular gland, adrenaline (100 pmol/l) has been shown to decrease the percentage of dye-coupled cells [Kanno et al., 1993], whereas isoproterenol was ineffective, so that the authors concluded that the mechanism was transmitted via action on the -adrenoceptors. This was supported since the adrenaline effect could be suppressed by coadministration of 10 pmol/1 phenoxybenzamine. 

Adrenaline and noradrenaline were oxidized in solution by hydrogen peroxide in the absence of metals via a free radical mechanism on irradiation. However, no aminochrome formation was observed.61... 

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