Misoprostol: Discovery, development, and clinical applications

Abstract

Misoprostol is a synthetic 15-deoxy-16-hydroxy-16-methyl analog of PGE1, and the first prostaglandin to be registered for the treatment of peptic ulcer disease. Misoprostol is a safe and well-tolerated drug that exerts potent gastric antisecretory effects and mucosal protective actions on the gastric and duodenal mucosa. In a dosage of 800 micrograms daily in two or four divided doses, misoprostol produced rates of complete ulcer healing in both gastric and duodenal ulcer patients significantly superior to placebo and comparable to H2 receptor antagonists. The major adverse effect is diarrhea in about 10% of patients, but this is usually mild and self-limiting. Misoprostol possesses uterotonic activity and should not be used in pregnant women or those who wish to become pregnant. Misoprostol effectively heals and prevents NSAID-induced gastropathy, a therapeutic need previously unserved. Due to its mucosal protective properties, misoprostol may have advantages over antisecretory drugs in the compromised patient who is a chronic smoker or alcohol user, in refractory duodenal ulcer patients, in recurrent ulcer, and in emergency use for acute upper GI bleeding. Misoprostol's tissue-protective effects may also extend to other therapeutic areas.

Signaling pathway of ginsenoside‐Rg1 leading to nitric oxide production in endothelial cells

“…The PI3K/Akt pathway is known as one of the candidates that are capable of activating eNOS directly [18]. In the present study, phosphorylation of eNOS and NO production were abolished by the inhibitors/antagonists: RU486 [19], LY294,002 [20], or SH-6 [21], whilst ICI182,780 had no effect. Since RU486 can act as a progesterone receptor (PR) antagonist [22], siRNA targeting GR was used in HU-VEC in order to preclude the involvement of other NRs in the Rg1 induction pathway.…”

Misoprostol does not alter the pharmacokinetics of propranolol

“…6 In an earlier study2 we found that the AUC ofpropranolol increased both during and after cessation of concurrent treatment with misoprostol. Healthy volunteers took propranolol daily for 4 weeks and during the 2nd and 3rd of these weeks took misoprostol in addition.…”

Misoprostol—a Logical Therapeutic Approach to Gastroduodenal Mucosal Injury Induced by Non-Steroidal Anti-Inflammatory Drugs?

“…ethanol) which do not depend on acid for their action and against intestinal ulceration caused by indomethacin. These data suggest that misoprostol's protective effect is mediated through actions other than inhibition of gastric acid secretion (41).…”

“…T h e key modifications made to natural PGE, which produced the compound misoprostol, are shown in Fig. 1. T h e rationale for the development programme of misoprostol and details of its synthesis and stereochemistry are comprehensively described in a recent review (41).…”