02-Adrenergic agonist activity

Derivatives of phenylethanolamine substituted by a phenolic hydroxyl on the para position have been known for some time to exhibit 0-adrenergic agonist activity. As a consequence of this property, the compounds have proven useful as bronchodilators for the treatment of asthma (see Chapter 3). Since such sympathomimetic drugs tend to have undesired activity on the cardiovascular system in addition to the desired activity on the bronchii, considerable work has been devoted to the preparation of compounds that would show selectivity for the adrenergic receptors (02> that predominate in the lung. Attachment of the side chain to a heterocyclic aromatic phenol has been one avenue that has shown promise for achieving this selectivity. 

Prenalterol (73) interestingly exhibits adrenergic agonist activity in spite of an interposed oxymethylene... 

Prenalterol (73) interestingly exhibits adrenergic agonist activity in spite of an interposed oxymethylene group. The stereospecific synthesis devised for this molecule relies on the fact that the side chain is very... 

Dopamine itself has long been used as an inotropic agent in acute treatment of congestive heart failure. Both that compound and a number of its analogues have a positive action on contractility as a consequence of their adrenergic agonist activity. 

Mechanism of Action Fomis an active metabolite, desglymidodrine, an alpha, adrenergic-agonist. Activation of the arteriolar and venous vasculature, producing and increase in vascular tone and elevation of blood pressure. 

The toxic events of terbutaline overdose follow its -adrenergic agonist activity. The effects of terbutaline overdose are usually mild and benign however, they can be prolonged. Cardiovascular effects are usually limited to a sinus tachycardia and widened pulse pressure. Although there may be a drop in diastolic pressure, the systolic pressure is maintained by increased cardiac output from the tachycardia. Evidence of myocardial ischemia after terbutaline overdose has been infrequently reported. Transient hypokalemia may occur, caused by a shift of extracellular potassium to the intracellular space. A transient metabolic acidosis can be seen due to increased lactate production. Restlessness, agitation, and tremors are common in terbutaline overdose. 

Tolazoline and the structurally related imidazoline tetrahydrozoline may be H2 receptor agonists since tolazoline-induced acid stimulation in the dog can be blocked by burimamide, metiamide and cimetidine and both imidazolines induce characteristic -agonist effects on isolated guinea pig atria preparations which can be blocked by metiamideJ Clonidine, like the imidazolines, has a-adrenergic agonist activity... 

Jen T, Frazee JS, Schwartz MS, et al. Adrenergic agents. 8.1. Synthesis and p-adrenergic agonist activity of some 3-tert-butylamino-2-(substituted phenyl)-1-... 

Because of the widespread nature of adrenoceptors, nonselective P-agonists can produce many undesirable side effects. Therefore, before adrenergic agonists could become widely used in the treatment of asthma, some selectivity in action was needed. Whereas epinephrine and ephedrine have significant agonist activity at both a and P adrenoceptors, isoproterenol is a selective agonist at the P receptor (39). However, isoproterenol does not distinguish between the P and receptors and it is not active orally. 

A common strategy for treating chronic opiate addiction iavolves the substitution of methadone which can either be provided as maintenance therapy or tapered until abstinence is achieved. Naltrexone and buprenorphine [52485-79-7] have also been used ia this manner. The a2 adrenergic agonist clonidine [4205-90-7] provides some rehef from the symptoms of opiate withdrawal, probably the result of its mimicking the inhibitory effect of opiates on the activity of locus coerukus neurons. 

A special feature of the iris is its autonomic innervation. Sympathetic activation widens the aperture of the iris whereas impulses from the parasympa thetic nervous system decrease the aperture size. Therefore adrenergic agonists and anticholinergic compounds both increase the aperture of the iris, i.e., cause mydriasis, and antiadrenergic and cholinergic agonists decrease it, i.e., cause miosis. The iris can thus be considered an excellent mirror reflecting the balance of the autonomic nervous system in the body. " ... 

A compound closely related to classical adrenergic agonists in which the para hydroxy function is however replaced by an amino group has been investigated for its activity as a growth promoter in domestic animals. Acylation of the aniline derivative 26 with chloracetyl chloride will afford acetophenone 27 the amino-ketone 28 is obtained on reaction with isopropylamine. Removal of the protecting group (29) followed by reduction of the ketone affords cimaterol (30) 5J. 

As noted above, phenylethanolamines are usually p-adrenergic agonists, whereas phenylpropanolamines show antagonist activity. A small series of phenyl-ethanolamine blockers is, however, known. When the haloatom of u)-bromo-5,6,7,8-tetrahydro-2-acetonaphth-one (36) is displaced with isopropylamine and the... 

In contrast to this, there are no such structural constraints on a-adrenergic agonists or antagonists. Some of the most active a-sympathomimetic agents in fact contain an imidazoline moiety as part of the pharmacophore. The appropriate ring system can be... 

Recent work in our laboratory (Kompella, Mathias, and Lee, unpublished observation) has revealed that activation of the cAMP-regulated Cl channels in the conjunctiva also enhances the transcytosis of horseradish peroxidase. 8-Bromo-cAMP (a membrane-permeable analog of cAMP) and terbutaline (a p2-adrenergic agonist known to increase intracellular levels of cAMP in other epithelial tissues [238]), at 0.5 mM, were found to enhance the transport of 100 pg/ mL HRP from the mucosal side to the serosal side of the pigmented rabbit conjunctiva by a factor of 4 (Fig. 11). 

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