The native fluorescence of a molecule is a complex function of its quantum chemical properties that may include the energy of its pi electrons. Reports^1,2 show that the HMO energy of methoxylated amphetamines correlates positively with their hallucinogenic potency. We have, therefore. measured the native fluorescence, at maximum activation and emission frequencies, of a number of amphetamines to see if there was any correlation with their hallucinogenic potency³. This work was carried out independently in Iowa and Edinburgh.

The relative intensity of emission was calibrated in the results from the 2 centres by multiplying each of the Iowa results by the ratio of values for DOM for the 2 groups. (The results are expressed in arbitrary units.) The average of the 2 readings were then taken. The results are presented in Table I.

In some cases, and in particular when scanning the bromo substituted compounds, difficulty was encountered due to intense Raman scattering peaks. 2,3,4,5-tetramethoxy- and 3,4,5- trimethoxyamphetamine also showed this scattering effect. Thus, the excitation maxima is taken as the maximum absorption excepting the Raman peaks, and it is possible that an actual maxima may lie underneath but was not observable in our experimental arrangement. Water is one of the best solvents for observing Raman scattering and the use of some other solvent might eliminate this problem.

In the series of bromo methoxy substituted compounds the 3-bromo-4-methoxy- isomer has been found inactive in rats, whereas the 4-bromo-2,5-dimethoxy- isomer is believed to be active from results of preliminary screen in mice, but it has not been fully tested as yet.

The plot of log dose vs fluorescence (Figure) has been done using values for dose in millimoles. This gives a more accurate representation of relative potencies. These findings invite the following comments: The native fluorescence of amphetamine is much increased by adding 1 methoxy group. 2 methoxy groups had less effect than 1 (particularly the 2,3 compound) except for the 3,4- and 2,5- substitutions. 3 and 4 methoxy groups led to a progressive decrease in fluorescence except for the 2,4,5- compound where there was less reduction. Thus, there was good correlation between the degree of native fluorescence and hallucinogenic potency except for the 3,4-; 2,4,6- and 2,3,4,5- compounds. The former is a feeble hallucinogen and fluoresces strongly, and the latter two are both active hallucinogens and yet fluoresce only feebly. The hallucinogenic tryptamines, as well as LSD, are in general much more potent hallucinogens than these methoxylated amphetamines, and have a notably stronger native fluorescence. The 2,4,6- and 2,3,4,5- compounds may owe their activity, in spite of their low highest occupied molecular orbital (HMO) energy, to the fact that the 2,6 (and tetra) substitutions offer maximum protection against metabolic breakdown by amine oxidase, and the 4 substitution protects against 4-hydroxylation⁴.

The behavioural effects of the bromomethoxy compounds require further elucidation.