Biological Activity and Disposition of the Amphetamine Analogue 2-Aminopropylferrocene

Abstract

1. 2-Aminopropylferrocene (FIPA) was rapidly absorbed following intraperitoneal administration to mice. From 5 to 120 min after administration, liver FIPA concn. remained constant while blood concn. declined steadily (t_0·5 = 114 min). In contrast, brain concn. of FIPA did not reach max until 30 min after administration, and then declined slowly (t_0·5 = 194 min). The apparent vol. of distribution of FIPA was 5·5 1/kg, and high affinity of FIPA for tissue was suggested by brain and liver concn. tenfold greater than blood concn.

2. Mice treated with FIPA (3-30 mg/kg) showed no differences in loco-motor activity from saline injected controls. However, at 100 mg/kg FIPA elicited convulsive behaviour in most mice.

3. In contrast to amphetamine, which markedly increased the spontaneous beating rate of isolated pargyline-treated rat atria, FIPA exhibited only a dose-dependent depressant effect on atrial rate.

4. Rats excreted 56-71% dose of ³H-FIPA in their urine in the first 96 h after dosing. Fractionation of urine indicated a large number of radioactive metabolites which were devoid of iron, but 32-43% of the FIPA administered was excreted unchanged. In contrast to ferrocene and amphetamine, which in rat are extensively hydroxylated, conjugated and excreted, no metabolites of FIPA containing an intact ferrocene moiety were detected.

5. In vitro, FIPA significantly inhibited metabolism of the cytochromt P-450 substrates aminopyrine and p-nitroamsole, but had no effect on the flavoprotein-mediated N-oxidation of N, N-dimethyloctylamine.