Homologous N,N-dimethyl-phenylalkylamine oxides and N,N-dimethyl-diphenylalkylamine oxides were prepared. Their basicity and lipophilicity (octan-1-ol/H2O) were compared to those of the parent amines. In contrast to the amines, the basicity of all N,N-dimethyl-arylalkylamine oxides showed very limited pK(a) variations (range 4.65-5.01) with increasing chain length and number of Ph groups. The N-oxides in their neutral form had a log P-N value lower by 2.77 +/- 0.34 (n = 9) units than that of the parent amine. The log P-C of the cationic N,N-dimethyl-diphenylalkylamines was lower than that of their neutral form, with a decrement diff(log PN-C) that increased from 3.25 to 4.21 in the homologous series. Unexpectedly. the decrement diff(log PN-C) for the N-oxides was much smaller than for the tertiary amines, being 0.23 for the aliphatic N,N-dimethyl-pentylamine oxide, 0.47 +/- 0.13 for the phenylalkylamine oxides, and 0.80 +/- 0.07 for the diphenylalkylamine oxides. In fact, the protonated N-oxides had log P-C values that were quite comparable to those of the protonated parent amines. Because of the differences in basicity, the difference in distribution coefficients at physiological pH (log D-7.4) between a tertiary arylalkylamine and its N-oxide was 0.82 +/- 0.66 (n = 9). The pharmacokinetic implication is that N-oxygenation may have a smaller effect on the urinary excretion of tertiary amines than usually assumed