Effect of extended hypocholesterolemic drug treatment on peripheral and central nervous system sterol content of the rat.

Extended treatment of developing or adult rats with a variety of hypocholesterolemic drugs has shown that both the central nervous system (CNS) and peripheral nervous system (PNS) sterol content could be affected in both age groups by this type of treatment. Treatment of developing animals was begun at 5 days of age and continued for 45 days. Adult rats, 300 g at onset, were treated for 35 days. The influence of these drugs on PNS sterol composition has not been previously examined. Diazacholesterol administration caused an accumulation of desmosterol in the CNS and 7-dehydrodesmosterol and desmosterol in the PNS. Zuclomiphene induced a build-up of desmosterol in either tissue. Both of these drugs had a more pronounced effect on developing CNS and PNS than on adult CNS and PNS. Addition of AY-9944 or Triparanol to the zuclomiphene treatment of the developing animals reduced desmosterol accumulation but brought about a build-up of 7-dehydrocholesterol and 7-dehydrodesmosterol.