Relationship of the structure of mescaline and seven analogs to toxicity and behavior in five species of laboratory animals.

The effect of mescaline and of 7 mescaline analogs (3,4-dimethoxy- β -phenylethylamine; 3,4-methylenedioxy- β -phenylethylamine; 3,4-methylenedioxy- α -methyl- β -phenylethylamine; 3,4-methylenedioxy- α -ethyl- β -phenylethylamine; 3,4-dimethoxy- α -methyl- β -phenylethylamine; 3,4,5-trimethoxy- α -methyl- β -phenylethylamine; and 3,4-methylenedioxy- N,α -dimethyl- β -phenylethylamine) has been studied in the mouse, rat and guinea pig following ip administration and in the mongrel dog and rhesus monkey following iv administration. The LD50 value for each agent has been determined in each species. For 7 of the 8 drugs tested the LD50 value is significantly lower in the rat than in the mouse or guinea pig. A comparison of the observable signs of drug action in the dog and monkey shows the dog to be the preferred species for evaluating the effects of these agents. The relevant literature regarding the actions of the drugs has been reviewed. Modifications in the mescaline structure which are represented by the 7 analogs and which alter pharmacologic activity include: decreased potency following removal of the 5-methoxy group or N-demethylation, and increased potency following alpha substitution on the side chain or introduction of the 3,4-methylenedioxy group.