J. theor. Biol. (1981) 91,237-239 Possible Interactions Between Alkoxy

A persistent enigma among the centrally active, alkoxylated amphetamines lies in the ability of the paru-substituent to determine the qualitative nature of subjective experience in man. Using experimental evidence to assume the serotonin receptor as the site of action for alkoxylated amphetamines (Glennon, Liebowitz & Anderson, 1980), one can postulate that the 5-hydroxy and l-nitrogen of serotonin correspond to the 2 and 5 positions of the benzene nucleus (of the substituted amphetamines), respectively. Vari-ations in the 4-substituent among the 2,5-dimethoxy amphetamines show marked differences in qualitative effect (Snyder, Faillace & Hollister, 1967; Shulgin, Sargent & Naranjo, 1971). This phenomenon is of considerable significance in the area of medical applications, since in general compounds devoid of sensory-distorting characteristics are sought for experimental psychotherapy. Since it is difficult to envision that substituents on the benzene ring can confer significant differences (via electronic, as opposed to steric factors) in the conformational energies of the alkylamino side chai