The rate of N-demethylation of N,N-dimethylanilines and N-methylanilines by rat-liver microsomes is related to their first ionization potential, their lipophilicity and to a steric bulk factor

Abstract

1. The N-demethylation of a series of 12 p-substituted N,N-dimethylanilines, nine m-substituted N,N-dimethylanilines, one o-substituted N,N-dimethylaniline and four p-substituted N-methylanilines by rat-liver microsomes was studied.

2. For each compound, the apparent V_max and K_m values were determined and these parameters were correlated with their electronic, lipophilicity and steric bulk parameters reported in the literature.

3. Multi-parameter linear regression analysis showed a good correlation between log V_max and these parameters for the p-substituted N,N-dimethylanilines. A lower degree of correlation was observed with the meta-substituted N,N-dimethylanilines.