Action of MDL 646, a new synthetic prostaglandin, on gastric acid secretion of some experimental animals.

The new synthetic prostaglandin 11,15-dihydroxy-16-methyl-16-methoxy-9-oxo-prost-13-en-1-oic acid,methyl ester (8 alpha,11 alpha,15R,16R) (compound marked MDL 646), belonging to the 16-methyl-16-methoxy series, was tested for its activity on gastric secretion of different animal species and in different experimental conditions. In the dog provided with gastric fistula and Heidenhain pouch, MDL 646 (25 micrograms/kg by intragastric administration) caused a remarkable inhibition of the histamine- and bethanechol-induced acid secretion, an effect which was more evident in the main stomach than on the Heidenhain pouch. In the cat, but not in the dog, the compound inhibited not only the hypersecretion induced by histamine and bethanechol but also that induced by pentagastrin. However, in this case, high doses (50-100 micrograms/kg) had to be used to obtain a significant inhibition. Similar results were obtained with the perfused stomach of the anaesthetized rat in which the natural PGE2 appeared to be from 3 to 5 times less potent. In the conscious rat provided with gastric fistula MDL 646 (15 and 50 micrograms/kg) significantly inhibited spontaneous gastric secretion. Untoward reactions, represented by salivation and vomiting lasting 30 min, were experienced by some dogs following administration of 50-100 micrograms/kg of the synthetic prostaglandin. These data appear of considerable interest in view of the possibility of the use of MDL 646 also in humans.