THE COMPETITIVE INHIBITION OF THE N-DEMETHYLATION OF BUTYNAMINE BY 2,4-DICHLORO-6-PHENYLPHENOXYETHYLAMINE (DPEA)

¹ Lilly Research Laboratories, Indianapolis, Indiana

DPEA (2,4-dichloro-6-phenylphenoxyethylamine) the primary amine analog of Lilly 18947 was shown to be an effective inhibitor of liver microsomal demethylase. In the in vitro system, the inhibition of butynamine and meperidine N-demethylation was found to be competitive. It was concluded that the inhibitor and substrate compete for the same site on the enzyme and that in general the primary amine has a much greater affinity for the site than does the corresponding tertiary amine.

DPEA was also found to be active in vivo in blocking the N-demethylation of butynamine-N-methyl-C¹⁴ by the rat. The inhibition of the metabolism of butynamine resulted in the rapid excretion of the unmetabolized drug into urine.