Abstract

Alfaxolone and four related steroids were tested for porphyrin-inducing activity in chick embryo liver cells. Alfaxolone (3α-hydroxy-5α-pregnane-11,20-dione) and 3α-hydroxy-5α-pregnane-20-one which have both anesthetic and membrane-fluidizing properties were found to exhibit high potency in inducing porphyrin biosynthesis. The 3β-hydroxy compounds (3β-hydroxy-5α-pregnane-11,20-dione and 3β-hydroxy-5α-pregnane-20-one) and Δ6-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.