Adrenoceptor agonists Norepinephrine

Isoproterenol and epinephrine are potent P2-adrenoceptor agonists norepinephrine is a relatively weak P2-adrenoceptor agonist. Isoproterenol and epinephrine produce vasodilation in skeletal muscle, but norepinephrine does not rather it produces vasoconstriction through the aj-adrenoceptors. Isoproterenol,... 

Norepinephrine and epinephrine are potent a-adrenoceptor agonists, while isoproterenol, a synthetic... 

The effect of a given adrenomimetic drug on a particular type of effector cell depends on the receptor selectivity of the drug, the response characteristics of the effector cells, and the predominant type of adrenoceptor found on the cells. For example, the smooth muscle cells of many blood vessels have only or predominantly a-adrenoceptors. The interaction of compounds with these adrenoceptors initiates a chain of events in the vascular smooth muscle cells that leads to activation of the contractile process. Thus, norepinephrine and epinephrine, which have high affinities for a-adrenoceptors, cause the vascular muscle to contract and the blood vessels to constrict. Since bronchial smooth muscle contains p2-adrenoceptors, the response in this tissue elicited by the action of p2-adrenoceptor agonists is relaxation of smooth muscle cells. Epinephrine and isoproterenol, which have high affinities for p2-adrenoceptors, cause relaxation of bronchial smooth muscle. Norepinephrine has a lower affinity for p2-adrenoceptors and has relatively weak bronchiolar relaxing properties. 

The bronchi have a rich parasympathetic innervation but there is no sympathetic innervation of bronchial smooth muscle and all sympathetic effects are due to circulating adrenaline (epinephrine and noradrenaline (norepinephrine) acting on (32 adrenoceptors. Stimulation of these receptors mediates bronchodilatation by relaxation of bronchial smooth muscle. Beta-adrenoceptor agonists also have limited antiinflammatory actions. They inhibit mediator release from mast cells and may stimulate... 

Let us consider the molecular principles behind the two modes of inhibition. Fig. 3.5b shows the stmctures of the agonist (norepinephrine) and of the two inhibitors. With some imagination, one can spot the similarity between agonist and inhibitors, so that it is understandable that they all bind to the same site on the a-adrenoceptor. Tolazoline has no obvious reactive groups, and it will therefore bind non-covalently and reversibly. 

At a dosage of 5 mg/kg (i.v.), tetrandrine was found to inhibit the pressor action of norepinephrine release induced by electrical stimulation of spinal cord Tn-L2. However, tetrandrine (5 mg/kg, i.a.) did not obviously attenuate the hypertensive responses to norepinephrine (0.51-16.91 pg/kg, i.v.), indicating that the alkaloid did not affect a1-adrenoceptor-mediated vasoconstriction. Tetrandrine (5 mg/kg, i.a.) was found to decrease the pressor responses to norepinephrine (0.05 and 0.17 pg/kg, i.v.) and markedly reduce the dose-dependent hypertensive responses to a selective a2-adrenoceptor agonist (B-HT920, i.v.), suggesting that the alkaloid reduced a2-adrenoceptor-mediated vasoconstriction [321]. 

Figure 12.21 shows three sets of log (DR-1) values for the (S -adrenoceptor antagonist atenolol in guinea pig tracheae the data points were obtained by blocking the effects of the agonists norepinephrine, isoproterenol, and salbuta-mol. These were chosen because they have differing efficacy for (3i- versus (S2-adrenoceptors (see Figure 12.21). If a mixture of two receptors mediates responses in this tissue, then responses to the selective agonists should be differentially sensitive to the (i -adrenoceptor-selective antagonist. In the example shown in Figure 12.21, it is not immediately...

The major dired-ading adrenoceptor agonist drugs are described. The alpha agonist phenylephrine increases mean BP, has no effed on pulse pressure, and elicits a reflex bradycardia. Isoproterenol, a beta agonist, decreases mean BP, increases pulse pressure, and causes marked tachycardia. Cardiovascular effects of norepinephrine (NE) are similar to phenylephrine, but it is also a cardiac (i, adrenoceptor j activator. The cardiovascular effects of epinephrine (E) are betalike at low doses and alphalike at high j doses. 

Postsynaptic a-adrenoceptors have been characterized in afferent and efferent arterioles isolated from rabbit renal cortex [263]. In both the afferent and efferent arteriole selective a 1-adrenoceptor agonists produced concentration-dependent vasoconstrictor responses with the maximum responses being equal to that of norepinephrine. Selective a 2-receptor agonists had less of an effect. The a 1-receptor antagonist, prazosin, produced a rightward shift in the concentration-response curve to norepinephrine, while the selective a 2-receptor antagonist, rauwolscine had no... 

Epinephrine activates all adrenoceptors, whereas norepinephrine has minimal agonist activity at [J -adrenoceptors. This difference is important in anaphylaxis because adrenoceptor activation is needed to provide a bronchodilatory effect that will oppose the anaphylaxis-induced airway obstruction. The aj-adrenoceptor agonist effect of epinephrine opposes the anaphylaxis-induced vasodilation and, to some extent, the vascular leak (administration of fluid is also a cornerstone of the treatment of anaphylaxis), while the Pj-adrenoceptor agonist effect helps maintain cardiac output. 

Norepinephrine Adrenoceptor agonist prototype acts at P,- and all a-adrenoceptors used as vasoconstrictor. Causes reflex bradycardia. Tox ischemia, arrhythmias, HTN. 

Careful examination of the effects of a series of sympathomimetics by Ahlquist (21) led him to postulate the existence of at least two types of adrenoceptors, which he termed a and p. Realizing that adrenoceptor agonists were capable of causing either relaxation or contraction of isolated smooth muscles, he noted that although a compound like norepinephrine had potent excitatory actions but weak inhibitory actions, another catecholamine, isoproterenol, had potent inhibitory actions but weak excitatory actions. When a series of related compounds were tested for potency in various tissues, it was demonstrated that for the a-adrenoceptor,... 

Absence of one or both aromatic hydroxyl groups is associated with an increase in indirect sympathomimetic activity, denoting the ability of a substance to release norepinephrine from its neuronal stores without exerting an agonist action at the adrenoceptor (p. 88). 

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