A-Adrenoreceptor blocking

In vivo, studies with dopamine agonists must generally be performed using phenoxybenzamine or other a-adrenoreceptor blocking agents. In vitro, not only must a-blocking drugs be... 

Giardina, D., Brasili, L., Gregori, M.. Massi, M., Picchio, M.T., Quaglia, W., Melchiorre, C., 1989. Structure-activity relationships among prazosin-related compounds. Effect of piperazine ring replacement by an alkanediamine moiety on a,-adrenoreceptor blocking activity. J. Med. Chem. 32, 50-55. 

Guanoxan formed salts with many optically active acids, but could not be resolved in this way because they were too insoluble to recrystallize. However, its hydrolysis product, 2-aminomethylbenzodioxane, was resolved and converted to (+)-(91) and (-)-(91) the former of which carried most of the a-adrenoreceptor blocking activity although the isomers were equipotent as adrenergic neurone blockers [103],... 

Kobayashi, J., Ohizumi, Y., Nakamura, H., Hirata, Y, Wakamatsu, K., and Miyazawa, T. (1986) Hymenin, a novel a-adrenoreceptor blocking agent from the Okinawan marine sponge Hymeniacidon ssp. Bxperientia, 42,1064-1065. 

Now let us go back to methyldopa. The afore-mentioned experiments by HENNING and van ZWIETEN (21) indicated a central mode of action. HEISE and KRONEBERG (22), perfusing part of the third and the entire fourth ventricle of the brain in cats with methyldopa, a-me-thyldopamine and a-methylnoradrenaline were able to show a decrease in blood pressure. These effects were significantly blocked by pretreatment with yohimbine and to a lesser extent by phentolamine. These experiments support the concept of blood pressure lowering by an action on central a-adrenoreceptors. 

Pharmacology Carvedilol, an antihypertensive agent, is a racemic mixture in which nonselective -adrenoreceptor blocking activity is present in the S(-) enantiomer and -adrenergic blocking activity is present in both R(+) and S(-) enantiomers at equal potency. Carvedilol has no intrinsic sympathomimetic activity. 

Pazos A, Engel G, Palacios JM. Beta-adrenoreceptors blocking agents recognize a subpopulation of serotonin receptors in brain. Brain Res 1985 343 403-408. 

Correct answer = A. A bidirectional block can decrease arrhythmias caused by reentry. All antiarrhythmic drugs exert some negative inotropic effect and decrease cardiac output. The i side effects of this group of drugs are serious and include arrhythmias that can lead to sudden death. Some antiarrhythmic drugs affect K+ or Ca++ channels, or p adrenoreceptors. 

The newer selective alphaj-adrenoreceptor-blocking agents, such as trimazosin, doxasozin, and terazosin, display a pharmacologic profile virtually identical to that of prazosin, but pharmacokinetic differences between the various alpha,-blockers exist. 

The new compound (Xlll, AH 5158A) is particularly interesting because it combines significant 3-adrenoreceptor blocking activity with a-blocking activity both in animals and in man.52... 

Bufuralol is a nonselective (3-adrenoreceptor blocking agent of comparable potency to propranolol. It has proven to be effective in treating hypertension and is a potent nonselective p-adrenergic receptor antagonist. Similarly to the method described earlier in Scheme 57.9, an efficient chemoenzymatic synthesis of (/ )-bufuralol has been reported involving a DKR of the chlorohydrin key intermediate rac-44 (Scheme 57.10). ... 

The main product of the Hofmann elimination of atracurium is laudanosine, an alpha-adrenoreceptor blocking agent which causes hypotension. Moreover, laudanosine crosses the blood-brain barrier (in contrast to the parent compound) and may cause excitement and seizure activity which leads to an increase in anaesthetic requirement by 30%. Accumulation and corresponding problems with laudanosine arise only in infants and with prolonged application in ICUs. ° Laudanosine-caused hypotension is enhanced by histamine released from tissue stores as a side effect of atracurium. 

In medical practice, a-adrenoblockers are drngs that block a - and o -adrenoreceptors, and they are nsed relatively rarely. The most important effect of a-adrenoblockers is the dilation of blood vessels, for which they are nsed in various disturbances of peripheral blood flow, and hemorrhagic and cardiogenic shock, in which the typical effect is a spasm of the arterioles. 

It is important to note that selectivity is not absolute, and it depends on the administered dose. In large doses, selectivity is even and both subtypes of j3-adrenoreceptors are inhibited equally. In addition to blocking j3-adrenoreceptors, these dmgs affect the cardiovascular system in a different manner. 

These drugs are peripheral coronary vasodilating drugs with a-adrenoblocking activity that differ only in specificity to aj-adrenoreceptors. Unlike phenoxybenzamine and phentolamine (described above), they selectively block aj-receptors and have little affinity with Oj-adrenergic receptors. 

Ergotamine blocks a receptors. It has an inhibitory effect on the cardiovascular system. Ergometrine also has a high affinity to uterine a2 receptors, and it therefore influences uterine muscle activity. Ergometrine is used in the treatment of postpartum or postbortal haemorrhaging. Yohimbine blocks presynaptic a2 adrenoreceptors and increases the release of noradrenaline at sympathetic nerve endings. It may be used to increase heart rate and blood pressure and even in the treatment of severe cases of male impotency. 

Block alpha-adrenoreceptors in the brain stem, resulting in reduced sympathetic outflow from the CNS and a decrease in peripheral vascular resistance... 

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