Erowid References Database
Barfknecht CF, Nichols DE.
“Effects of S-(+)- and R-(-)-3,4,dimethoxyphenylisopropylamines in the rat”.
J Med Chem. 1972 Jan;15(1):109-10.
While much information is available about the structure- activity relationships of one-ring psychotomimetics related to mescaline,' no data on the relative potency of optical isomers has been reported. Since a cross-tolerance exists between LSD and mescaline-type compounds, it has been suggested that they act via the same mechanism. Both com- pounds are 0-arylethylamine derivatives. While most litera- ture views LSD as having the ethylamine side chain arising from the 3 position of the indole nucleus, a closer struc- tural analogy exists when the side chain is joined at the 4 position.
If this is a valid analogy in evaluating optically active mescaline-type agents, one might anticipate a priori that the isomer whose absolute configuration was the same as the C-5 position of (+)-LSD (natural, 5R, 8Rj4>' (1) would pos- sess the psychotomimetic activity. The absolute configura- tions of phenylisopropylamines are 5'-(t) (2) and I?-(-) (3), respectively.6 Schrecker' proved by total synthesis that (t)- and (-)-3,4-dimethoxyphenylisopropylamines (3,4- DMA) are S-(t) and I?-(-), respectively. On such a stereo- chemical basis, the R-(-)-3,4-DMA would be expected to have the mescaline-like actions. while its enantiomer, S-(+)- 3,4-DMA, would be expected to be much less active. In con- trast, unsubstituted phenylisopropylamine has its central effects primarily in the S-(t) isomer.
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