Studies on the luteolytic activity of MDL-646, a new gastroprotective PGE 1 analogue, in the hamster

Abstract

MDL-646, 11,15-dihydroxy-16-methyl-16-methoxy-9-oxo-prost-13-en-1--oic acid methyl ester, is one of the most active members of a new class of PGE 1 analogues with potent gastric cytoprotective and antisecretory activity. The potential luteolytic activities of MDL-646 and its corresponding PGE 2 derivative, L 14224 were assessed from their ability to terminated pregnancy and to reduce plasma progesterone levels in the hamster. PGE 1 and PGE 2 were used as reference compounds. The biological and biochemical data clearly demonstrate that these 16-methyl-16-methoxy PGE derivatives, given s.c. or p.o. either once or for 3 days, have no luteolytic effects up to a daily dose of 2–2.5 mg/kg, and are therefore at most 1 2 to 1 4 as luteolytic as the parent natural PGEs. The dissociation between gastroprotective and luteolytic activity was interpreted to indicate that these new PGE derivatives have a specific action.