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Molecular Pharmacology, Vol 18, 144-147, Copyright © 1980 by the American Society for Pharmacology and Experimental Therapeutics

Association between the Membrane-Fluidizing Properties and Porphyrin-Inducing Activity of Alfaxolone and Related Steroids

I. R. NEILSON 1, M. A. SINGER 1, and G. S. MARKS 1

1 Departments of Pharmacology and Medicine, Queen‘s University, Kingston, Ontario, Canada

Alfaxolone and four related steroids were tested for porphyrin-inducing activity in chick embryo liver cells. Alfaxolone (3agr-hydroxy-5agr-pregnane-11,20-dione) and 3agr-hydroxy-5agr-pregnane-20-one which have both anesthetic and membrane-fluidizing properties were found to exhibit high potency in inducing porphyrin biosynthesis. The 3beta-hydroxy compounds (3beta-hydroxy-5agr-pregnane-11,20-dione and 3beta-hydroxy-5agr-pregnane-20-one) and Dgr6-alfaxolone, which are nonanesthetic and produce less disorder of phospholipid bilayers, were considerably less potent as porphyrin-inducing compounds. These findings provide strong support for the concept that at least some porphyrin-inducing drugs act by disorganizing membrane lipids.

Submitted on September 21, 1979
Accepted on January 11, 1980




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