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Journal of Pharmacology And Experimental Therapeutics, Vol. 176, Issue 1, 83-92, 1971
Copyright © 1971 by American Society for Pharmacology and Experimental Therapeutics

DISTRIBUTION OF HEXAMETHONIUM AND OTHER QUATERNARY AMMONIUM COMPOUNDS IN CARTILAGE

KHURSHEED ASGHAR 1 and LLOYD J. ROTH 1

1 Department of Pharmacology, University of Chicago, Chicago, Illinois

N-methyl-C14- and H3-labeled hexamethonium was administered to rats and mice in a dose of 10 to 30 mg/kg. Tissue sections for whole body and cellular autoradiography were cut from animals sacrificed at various intervals after injection. In contrast to the distribution pattern of most drugs hexamethonium was found to he preferentially accumulated in certain avascular cartilaginous tissues, including those of intervertebral discs. epiphyseal and articular cartilages of hip. knee and other joints. costal and articular cartilage of the ribs, circular cartilage of trachea and nasal and ear cartilages. On the other hand, the compact bone itself or the bone marrow of femur and other bones showed little radiodensity in the autoradiograms. A similar pattern of distribution is observed after C14-decamethonium. Cellular autoradiograms and histochemical studies showed localization of the labeled hexamethonium in areas rich in acid mucopolvsaccharides. Hexamethonium was also found, in vitro, to bind strongly to chondroitin sulfate. It is hypothesized that the diquaternary ammonium compounds, under physiologic conditions, are bound to the polyanionic mucopolysaccharide components of cartilaginous tissue.

Submitted on July 14, 1970
Accepted on September 1, 1970




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Copyright © 1971 by the American Society for Pharmacology and Experimental Therapeutics.