A-Adrenoreceptors

Choi, Y. W. Rogers, J. A., The liposome as a model membrane in correlations of partitioning with a-adrenoreceptor against activities, Pharm. Res. 7, 508-512 (1990). 

The answer is a. (Katzung, p 499.) Of the listed a n tide press ants, only amitriptyline, a tricyclic, causes adverse effects related to blockade of muscarinic acetylcholine receptors. Both trazodone and amitriptyline cause adverse effects related to a-adrenoreceptor blockade... 

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. 

The utility of 1,3-tertiary-quatemary stereocenters was highlighted in the 7-step transformation of adduct 92 to diol 93. Diol 93 was previously demonstrated used by Ohfune [62] as a key intermediate in a 22-step syntheses of manzacidin A, a bromopyr-role alkaloid with interesting pharmacological profile as an a-adrenoreceptor blocker and serotonin antagonist (Scheme 19). 

The lesser the degree of substitution at the amino group, the greater selectivity of the compound in activating a-adrenoreceptors, and vice versa, an increase in volume of substituents at the primary amino group adds to the selectivity in relation to )3-receptors. 

Norepinephrine is the primary neurotransmitter produced and released by adrenergic neurons, and in literature it is also described as and called (-) noradrenaline or levarterenol. This vasopressor catecholamine reduces both the resistance and capacity of blood vessels by stimulating a-adrenoreceptors and having a direct cardiostimulatory effect, which is accomplished by activation of )3i-adrenoreceptors. Norepinephrine exhibits significantly less activity than epinephrine as a drug for widening blood vessels through the activation of jSj-adrenoreceptors. Elevation of both stylistic and diastolic blood pressure is a typical reaction to intravenous introduction of norepinephrine. 

This synthetic drug has both chemical and pharmacological similarities to norepinephrine. A characteristic quality of phenylephrine is the distinctly expressed selectivity to a-adrenoreceptors, especially aj-adrenoreceptors. Although phenylephrine increases the contractibility of blood vessels, in practical terms it is not considered a cardiostimulant. 

Dopamine is found in every sympathetic neuron and ganglion in the CNS. As a drug, and in addition to stimulation of dopaminergic receptors, dopamine indirectly stimulates both a- and )3-adrenoreceptors. Dopamine also causes a release of endogenous norepinephrine. The mechanism of action is based on the excitatory effect on )3-adrenoreceptors (in low and moderate doses), as well as on a-adrenoreceptors (in large doses). It has a positive inotropic effect on the heart, increases blood supply, selectively widens renal and mesenteric blood vessels, does not elevate blood pressure, and slightly increases the frequency of heartbeats. 

Adrenoblocking drugs are classified as a-adrenoblockers, j8-adrenoblockers, and adrenergic neuron blockers depending on the response brought about in the organism. a-Adrenoreceptors cause dilation of peripheral blood vessels, and a few of them relax smooth muscles. 

Although several factors can influence the flow of blood through the coronary vessels, the most important of these is the local production of vasodilator metabolites that results from stimulation-induced increased work by the heart. a-Adrenoreceptors and -adrenoceptors in the coronary vascular beds do not play a major role in determining the vasodilator effects of the administration of epinephrine or norepinephrine. 

Of the clinically tested new antipsychotics, ziprasidone has the highest 5-HT2A/D2 receptor-affinity ratio. Ziprasidone is an antagonist at the a -adrenoreceptor, but its affinity is half that of its D 2 affinity. In addition, compared with its affinity for D 2 and 5-HT2A receptors, ziprasidone has a relatively low affinity for histamine receptors (pKJ = 7.33). In vitro, ziprasidone is a moderately potent inhibitor of neuronal reuptake of norepinephrine, serotonin, and, to a lesser extent, dopamine. This property is shared with some antidepressants, and contrasts with risperidone, which is inactive at all three monoamine uptake sites. 

There are two principal groups of receptors for epinephrine and NE, so-called adrenoreceptors, which are divided into a- and P-adrenoreceptors. a-adrenoreceptors are subdivided into oti and oc2, whereas the P-adrenoreceptors into Pi, P2 and P3. All the adrenoreceptors are coupled to different G protein subtypes. More specifically, oci-adrenoreceptors is coupled to Gq, a2-adrenoreceptors to Gi, and all the P-adrenoreceptors to Gs. Briefly, activation of Gs and G, stimulates and reduces the production of cAMP, respectively. cAMP functions as a second messenger that can activate the protein kinase A (PKA), which in turn, can transfer the signals to the nucleus. 

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... 

Prazosin (hydrochloride), 2-[4-(fur-2-oyl)piperazin-l-yl]-6,7-dimethoxy-4-quinazolinamine, a-adrenoreceptor antagonist antihypertensive [19216-56-9],... 

Sympathomimetic agents, such as brimonidine tartrate, apraclonidine, adrenaline and dipivefrine hydrochloride, which is a prodrug for adrenaline), act on a-adrenoreceptors to induce dilation of the veins to reduce IOP. They also induce mydriasis (dilation of the pupils). Adrenaline may reduce the rate of formation of the aqueous humour, which in turn reduces the IOP it may also increase the outflow through the trabecular meshwork. Stimulation of alpha-2-adrenoreceptor (c -adrenoreceptor) by drugs such as brimonidine and apraclonidine on the adrenergic neurons supplying the ciliary body can also result in reduction of secretion of aqueous humour. 

Adrenaline is only capable of producing platelet aggregation in the presence of other platelet agonists (Steen cr of, 1993 Lanza et al, 1988), and is therefore not a tme agonist. Platelets have stimulatory Uj adrenoreceptors and inhibitory p adrenoreceptors, but the adrenoreceptors predcnnhiates. The adrenoreceptor is coupled via G proteins to adenylyl cyclase, while ffie a, adrenoreceptor (present in about 30 %) has Ireen proposed to be... 

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