CNS stimulant properties and physiologic disposition of Β,Β-difluorophenylethylamine in mice

,-Difluorophenylethylamine, because of the strong electrophilic nature of the fluorines, is a much weaker base than is phenylethylamine. The pK for the difluoro compound is 6.75 compared to 9.55 for phenylethylamine. At physiologic pH, difluorophenylethylamine exists primarily as a neutral molecule, whereas phenylethylamine is almost entirely cationic. Difluorophenylethylamine caused increased locomotor activity in mice, and its effects were enhanced by a monoamine oxidase inhibitor (tranylcypromine) as were the effects of phenylethylamine. Comparable levels of difluorophenylethylamine and phenylethylamine in brain appeared to lead to equivalent increases in locomotor activity. At doses above those giving the maximum increase in locomotor activity, behavioral differences between phenylethylamine and difluorophenylethylamine were observed. Difluorophenylethylamine localized in adipose tissue to a greater degree than in other organs; it disappeared from adipose tissue and from brain with a physiologic half-life of 8 min in mice.