Effects of E prostaglandins, diphenoxylate and morphine on intestinal motility in vivo.

The mechanism of the gastrointestinal motility effects of diphenoxylate and morphine in preventing E prostaglandin (PG) diarrhea was investigated. Duodenal motility studies were conducted in the anesthetized dog. Two contractile force transducers were oriented to record contractions from both the circular and longitudinal muscles. In some experiments the basic electrical rhythm (BER) was also recorded. Blood pressure was monitored from the femoral artery and drug injections were made in the femoral vein. Diphenoxylate shared with morphine the capacity to stimulate circular muscle contractions which correlated with the appearance of spike potentials on the BER. Prostaglandin E1 methyl ester (PGE1ME) showed marked relaxation of the circular muscle and abolishment of spike potentials. PGE1ME also blocked the stimulatory effects of diphenoxylate and morphine on the circular muscle. PGE1ME and PGE2 were found to be equally potent in producing diarrhea in mice. Diphenoxylate and morphine were found to be equally potent in inhibiting PG's diarrhea. These studies suggest that the constipating actions of diphenoxylate and morphine are a consequence of the increased circular muscle activity of the intestine.