THE BIOTRANSFORMATION, EXCRETION, AND DISTRIBUTION OF THE ANTICHOLINERGIC QUATERNARY AMMONIUM COMPOUND BENZOMETHAMINE [N-DIETHYLAMINOETHYL-N'-METHYL-BENZILAMIDE METHOBROMIDE (MC 3199)] AND ITS TERTIARY AMINE ANALOGUE (MC 3137) AND RELATED COMPOUNDS IN ANIMALS

¹ Department of Pharmacology, Tufts College Medical School, Boston, Massachusetts

The biotransformation, excretion and tissue distribution of benzomethamine and its tertiary amine analogue have been studied in animals. A number of other monoquaternary ammonium compounds have also been included in this study. The urinary excretion of the quaternary ammonium compounds was found to proceed rapidly, but the recovery after oral administration ranged from 1-8 per cent whereas that after intravenous administration ranged from 17-50 per cent. The urinary excretion of the tertiary analogue of benzomethamine was slow and very incomplete after both oral and intravenous administration. Benzomethamine and its tertiary analogue were found to be metabolized by the liver of rats, mice and dogs, the tertiary compound being metabolized much more rapidly.

Benzomethamine and the other quaternary ammonium compounds examined were found to be distributed primarily in the tissues concerned with excretion (the liver, kidney and small intestine) and were not found in heart, brain or muscle. On the other hand, the tertiary analogue of benzomethamine had a more general type of tissue distribution.

A large portion, 50-70 per cent, of the total recovered after intravenous administration of the monoquaternary compounds was excreted in bile. Little or none of the corresponding tertiary analogues was found in bile.