LABORATORY STUDIES OF 1-METHYL-4-PIPERIDYL BIS(P-CHLOROPHENOXY) ACETATE (SAH 42-348) - A NEW HYPOLIPIDEMIC AGENT

The hypolipidemic properties of 1-methyl-4-piperidyl bis(p-chlorophenoxy) acetate (SaH 42-348) in the male Wistar rat have been described. This agent is eight to nine times more active on a weight for weight basis than chlorphenoxy isobutyric acid ethyl ester (CPIB) (Atromid-S), and in common with CPIB lowers the levels of all major classes of serum lipid. No increase in liver lipid content was seen in animals treated with SaH 42-348, although hepatomegaly was seen after treatment with SaH 42-348 or with CPIB. Evidence is presented suggesting that the mechanism of action of SaH 42-348 in lowering serum cholesterol in the rat differs from that of CPIB. Thus, it was not possible to demonstrate that SaH 42-348 inhibited cholesterol biosynthesis in vivo from 1-14C acetate, while the inhibitory effect of CPIB was readily demonstrated. In addition, n- propylthiouracil (PTU) inhibited the hypocholesterolemic activity of CPIB in both normolipemic and hyperlipemic rats, whereas the activity of SaH 42-348 was unaffected by PTU. © 1969.