The Fate of an Experimental MAO Inhibitor, N-Cyclopropyl-2-Chlorophenoxyethylamine (Lilly 51641) in the Rat and in Man

Abstract

1. In vivo metabolism studies have shown N-cyclopropyl-2-chlorophenoxy-ethylamine (Lilly 51641) to be extensively metabolized in the rat. Those metabolites identified include 2-chlorophenoxyacetic acid, N-cyclopropyl-4-hydroxy-2-chlorophenoxyethylamine and 4-hydroxy-2-chlorophenoxyethanol, together with a number of minor products. The major route of elimination of these metabolites is through the kidney.

2. The major in vitro metabolites of Lilly 51641 have been identified as 2-chlorophenoxyethylamine, 2-chlorophenoxyacetaldehyde, 2-chlorophenoxyacetic acid and 2-chlorophenoxyethanol. It thus appears that this drug is metabolized by the following sequence: N-dealkylation, deamination and aldehyde oxidation or reduction.

3. Aromatic hydroxylation was found to be an independent but important mechanism involved in the metabolism of Lilly 51641.

4. Human urinary metabolites of Lilly 51641 were separated and identified. The nature of these metabolites indicated that the same mechanisms of detoxication were involved in the biotransformation in the human as were involved in the rat.

5. The major human urinary metabolite was 4-hydroxy-2-chlorophenoxy-acetic acid.