It is known that neither tryptamine nor serotonin crosses the blood-brain barrier easily. As shown in this paper, methylation or ethylation of the amino group of tryptamine (D-MT, DET) promotes penetration into the central nervous system. Methylation of the hydroxyl group (5-methoxytryptamine) of serotonin does not help penetration, whereas methylation of the hydroxyl and amino group (5-methoxy-DMT) of serotonin promotes penetration through this barrier. Thus, both the free hydroxyl and amino group of indolealkyls seem to impair penetration into the brain. This is different from the catecholamines where only a free hydroxyl but not a free amino group impairs penetration into the brain; dopamine does not cross the blood-brain barrier, whereas methylation of the hydroxyl groups (3,4-dimethoxyphenylethylamine) promotes penetration, in spite of the free amino group.