Abstract

The physiological disposition of hexamethonium, its sulfonium analogue, its monoquaternary derivative, three symmetrical derivatives and one asymmetrical derivative have been studied in animals.

Hexamethonium, the sulfonium analogue, and the monoquaternary derivative undergo no biotransformation in the intact mouse.

All the compounds studied are poorly absorbed from the small intestine but hexamethonium continues to be absorbed over a longer period of time.

Hexamethonium can be found in blood for at least 1 hour following an intravenous dose of 30 mg/kg and is distributed rather uniformly to all tissues including muscle and some adipose tissue depots, but not to brain tissue. The symmetrical derivatives have a tissue distribution qualitatively similar to that of hexamethonium with the important exception of the sulfonium derivative which is distributed quite readily to brain tissue. The asymmetrical derivative, IN 181, differs from hexamethonium in that it is not found in muscle or adipose tissue but is detected in brain tissue. The monoquaternary derivative also resembles hexamethonium in its tissue distribution except that it concentrates to some degree in the liver and its level in the blood decreases more rapidly.

Biliary excretion does not represent a major pathway of elimination for any of the compounds. Following an oral dose, about 40% of hexamethonium is excreted in the urine within 5 hours but only about 8% of its monoquaternary derivative is excreted in the same period.

The similarities and differences in physiological disposition among the various groups of onium compounds are discussed.