Metabolism of 7,8-dichloro-1,2,3,4-tetrahydroisoquinoline, a phenylethanolamine N-methyltransferase inhibitor. II. Species difference in metabolism and synthesis of its metabolites

Abstract

1. 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline (DCTQ), a potent reversible inhibitor of phenylethanolamine N-methyltransferase, was well absorbed, readily metabolized and excreted mainly in urine.

2. Its pathways of metabolism in rats and dogs were markedly different. In the dog, N-methylation was followed by N-oxidation to give the corresponding N-methyl-N-oxide as the final metabolic product. This was not observed in the rat.

3. In the rat, major pathways are aromatization of DCTQ to the corresponding isoquinoline and subsequent hydroxylation in the hetero ring to all three possible isomeric hydroxy-isoquinolines.

4. Authentic metabolites were synthesized for comparison with metabolites isolated from urine.