Phenylpropylamines

Phenylpropylamines are another stmctural class of receptor agonist. The two most important members are methadone [76-99-3] C2 H2yNO, (8) (17), discovered in Germany during World War II, and propoxyphene [469-62-5] C22H22NO2, (9). 

FIGURE 4.24 Adsorption chromatography of small molecules with a TSK-GEL G2500PWxl column. Column TSK-GEL G2500PWxl, 6 /tm, 7.8 mm X 30 cm. Sample (I) phenylacetic acid. (2) 3-phenylpropionic acid, (3) 4-phenylbutyric acid, (4) benzylamine, (5) 2-phenylethylamine, (6) 3-phenylpropylamine, (7) benzyl alcohol, (8) 2-phenylethanol, and (9) 3-phenyl-1 -propanol. Elution 0.1 M NaCIO, in water. Flow rate 2.0 ml/min. Temperature 65 C. Detection UV at 215 nm. 

The very slow onset of action and side effects which follow from the anticholinergic side effects characteristic of the tricyclic antidepressants has led to a continuing effort to find replacements from other structural classes which might thus be devoid of this defect. A series of alkoxy phenylpropylamines has been investigated extensively in this search for non-tricyclic antidepressants. The most recent analogue, tomoxetine (69), is accessible by the same route [15] used to prepare the earlier analogue, nisoxetine, in which methoxyl replaces the ortho methyl group. 

Fuller, R.W. Perry, K.W. and Molloy. B.B. Effeet of 3-(p-trifluoromethyl-phenoxy)-N-methyl-3-phenylpropylamine on the depletion of brain serotonin by 4-chloroamphetamine. J Pharmacol Exp Ther 193 796-803, 1975b. 

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