(1) 2,4-dihydroxy-N,N'-dimethylbenzylideneaniline (HNB) [illegible] 7.2 H+ (mmol/dose) in an acetonitrile solution (d=0.65) POP 3.9 O* (mmol/dose) "" (d=0.8) SOP 3.9 N+ (mmol/dose) "" (d=0.4) JOP 9.2 X- (mmol/dose) "" (d=0.65) GOP 12.8* (d=0.8) YOR 12.8* (d=0.65) POP 12.8* (d=0.4) OHP 17.3 F- (d=0.65) SOP [illegible] This was done in an attempt to test the hypothesis that HNB is more potent than its metabolites, but this was not confirmed by our results. In order to test this hypothesis we used a new set of conditions which allowed us to measure concentrations directly with the HPLC. The results are summarized in Table 1. We found that HNB did not show any significant effect on either the rate or extent of drug clearance in vivo. However, when tested at higher doses (20 mg/kg), it appeared to have some inhibitory effects on liver enzyme activity. This suggests that while HNB may be less active than its metabolites under normal physiological conditions, it could potentially become a useful therapeutic agent if administered at high enough concentrations. Table 1: Effect of various compounds on rat liver microsomal cytochrome P450 activity Compound | Concentration (µM) | Activity (% control) ---|---|--- [illegible] | [illegible] | [illegible] HNB | [illegible] | [illegible] Metabolite A | [illegible] | [illegible] Metabolite B | [illegible] | [illegible] [illegible] 2.4-dihydroxy-N,N'-dimethylbenzylideneaniline (HNB) [illegible] 137-180 mg/kg, 3 days 137-180 mg/kg, 5 days 111-173 mg/kg, 2 days 111-173 mg/kg, 5 days [illegible]