Agonist Replacement

Partial agonists are in early developmental stages. Agonist replacement is an attractive strategy, because of the successs of methadone and buprenorphine in opioid dependence. 

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. 

The main mineralocorticoid agonist in humans is aldosterone. Additionally, cortisol, corticosterone, and DOC have also mineralocorticoid agonistic activity. The synthetic steroid fludrocortisone (9a-fluorocorti-sol) is extremely potent and usually chosen for replacement mineralocorticoid therapy. In contrast, aldosterone and DOC are not useful in oral therapy due to rapid degradation in liver after absorption. 

Monitor serum potassium in patients receiving high-dose or continuous nebulization of a short-acting p2-agonist. Serum potassium concentrations should be obtained upon admission, and if hypokalemic, every 4 hours (after each 30 to 40 mEq or mmol of replacement) until the patient s potassium is stable. Potassium should be monitored every 3 to 6 months after discharge. 

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