1. Ferrocenylisopropylamine (FIPA) inhibits the elimination of ampheta mines in rat. The half-life of isopropylamphetamine was increased from approx. 30 to 85-100 min after administration of FIPA.2. With isolated, perfused, rat liver, the half-lives of isopropylamphetamine, biamphetamine and benzylamphetamine were increased from 5-20 min to about 200 min by equimolar amounts of FIPA, indicating that the. prolonging effect of FIPA is due to iriterference at the metabolic level.3. Experiments with hepatic microsomal suspensions demonstrated that FIPA competitively inhibits the oxidativé N-dealkylation of isopropylampheta mine ; the Ki of FIPA is 4-1 x 10_* M.4. Binding of isopropylamphetamine and FIPA to cytochrome P-450 was studied using hepatic microsomes of phenobarbital-treated rats. Isopropylamphétamine caused a type I, and FIPA a type II difference spectrum ; FIPA showed a much higher binding affinity (/Cs= 1-24 x 10 8 m) than isopropyl amphetamine (i£g = 0-96 x 10~3 m ). FIPA acts as a modifiér of the spectral changes indüced by isopropylamphetamine.5. Results suggest that the competitive inhibition of the N -dealkylation of Ar-aikylamphetamines, and thus the prolonging of their action, by FIPA is related to competition for binding to cytochrome P-450.
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