Behavioural Effects of some Derivatives of Amphetamine and LSD and their Significance
Nature May 16, 1970 J. R. Smythies, J. Beaton, F. Benington et al.
N,N-dimethyl derivatives of hallucinogenic amphetamines are far less potent than the parent compounds. In rats, 4-methoxyamphetamine produced a typical hallucinogenic profile at 3 mg/kg, but its N,N-dimethyl derivative was totally inactive at 25 mg/kg. Similarly, DOM (2,5-dimethoxy-4-methyl amphetamine) was active at 2.5 mg/kg, while its N,N-dimethyl derivative was inactive at 20 mg/kg. These results suggest that the amino group is necessary for activity and that these compounds likely bond using their nitrogen atoms. The activity of methoxylated amphetamines correlates more with quantum chemical properties, such as Hückel molecular orbital energies and native fluorescence, than with steric properties.