Phenethyl and Phenylpropylamines

By the turn of the century the theory of chemical mediation of physiologic responses had gained some currency. There ensued in some laboratories an intense search for endogenous chemical modifiers of bodily responses. The first such agent to be isolated from mammalian tissue was the ubiquitous hormone, epinephrine—at that time known as adrenaline. This compound has played an important role in pharmacology as well as in medicinal chemistry. 

Epinephrine itself does find some use in clinical medicine. The drug is used in order to increase blood pressure in cases of circulatory collapse, and to relax the bronchial muscle in acute asthma and in anaphylactic reactions. These activities follow directly from the agent s physiologic role. The biogenetic precursor of epinephrine, norepinephrine, has activity in its own right as a mediator of sympathetic nerve action. (An apocryphal story has it that the term nor is derived from a label seen on a bottle of a key primary amine in a laboratory in Germany N ohne 

Removal of one of the aromatic hydroxyl groups gives an agent similar to epinephrine in its effects but with longer dura- 

Lion of action. The largest use of this drug, however, depends on its vasoconstricting action phenylephrine is used extensively as a nasal decongestant due to its ability to constrict the blood vessels in mucous tissue on local application. In one published 

The isomer of isoproterenol in which both aromatic hydroxyl groups are situated meta to the side chain also exhibits bron-chiodilating activity. Oxidation of 3,5-dimethoxyacetophenone by means of selenium dioxide affords the glyoxal derivative (15). Treatment of the aldehyde with isopropylamine in the presence of 

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