Steric and Electronic Relationships among Some Hallucinogenic Compounds
Proceedings of the National Academy of Sciences September 1, 1970 Sungzong Kang, Jack Peter Green 64 citations
A common mechanism may underlie how structurally different hallucinogens—LSD, indolealkylamines, and methoxylated amphetamines—interact with their receptor. In LSD, the aromatic benzene ring A and the N-6 nitrogen are essential for activity; these sites may react with the receptor. The conformations of amphetamines and indolealkylamines position their aromatic ring and alkylamino nitrogen to align with LSD's ring A and N-6. Ring A may form a π-molecular complex with the receptor, supported by a correlation between hallucinogenic activity and the energy of the highest occupied molecular orbital. The N-6 nitrogen and its sterically congruent counterparts may form an n-π* or n-σ* donor-acceptor complex. Additional groups (methoxy, hydroxyl, pyrrole ring) contribute favorable orbital energy.