Studies on the luteolytic activity of MDL-646, a new gastroprotective PGE1 analogue, in the hamster

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 PGE1 analogues with potent gastric cytoprotective and antisecretory activity. The potential luteolytic activities of MDL-646 and its corresponding PGE2 derivative, L 14224 were assessed from their ability to terminate pregnancy and to reduce plasma progesterone levels in the hamster. PGE1 and PGE2 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.