Adrenoreceptor Blocking Agents

The P-adrenoceptor blocking agents (or P-blockers) have received an overwhelming cognizance in the therapeutic armamentarium in the past four decades that they have been judiciously classified into the following three categories, namely  

These three specific types of P-blockers shall now be treated individually in the sections that follows  

The first main objective towards the exploratory development of these agents was to accomplish selectivity for P-receptors with respect to a-receptors. 

The various stages that were essentially followed in a sequential manner for the development of propranolol, a predominant candidate drug of this category are as stated under  

P -blocker to be employed profusely as an wonderful drug for the eontrol, management and treatment of angina, high BP, and arrythmias. 

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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... 

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

Tab. 4.16 Structures of P-adrenoreceptor-blocking agents. (Reprinted from Tab. 1 of ref. 54 with permission from the American Chemical Society)...

Peripherally acting antiadrenergic drugs Direct vasodilation (postsynaptic ai-adrenoreceptor blocking agents) No change in GFR and RBF... 

Activation of dopaminci (DA ) and dopamine2 (DA2) receptors reduces blood pressure. DA is not useful as an antihypertensive agent because of its alpha-adrenoreceptor activity. However, extensive studies in patients with hypertension have demonstrated that, after administration of alpha-adrenoreceptor-blocking agents, arterial pressure is decreased with maintenance or improvement of renal blood flow. 

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. 

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). ... 

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. 

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. 

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. 

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