POTENCY AND SELECTIVITY OF METHYL ANALOGUES OF PROSTAGLANDIN E2 ON RAT GASTROINTESTINAL FUNCTION

Abstract

1 The potency and selectivity of action of prostaglandin E₂ and its (15S)- or (15R)-15 methyl and 16,16 dimethyl analogues on gastrointestinal function have been studied in the rat. 2 The (15S)-15 methyl and 16,16 dimethyl analogues were 40 times as active as prostaglandin E₂ in inhibiting pentagastrin-stimulated acid secretion on intravenous administration to the anaesthetized rat, and 100 times as active on subcutaneous injection to the chronic fistula rat. 3 In antisecretory doses, the analogues, like prostaglandin E₂, caused bile reflux and, in higher doses, profuse diarrhoea. 4 The (15S)-15 methyl and 16,16 dimethyl analogues were at least 30 times as active as prostaglandin E₂ in causing changes in intestinal intraluminal pressure in vivo, but were equipotent on isolated smooth muscle. 5 In equivalent antisecretory doses, the methyl analogues had little effect on systemic arterial blood pressure and resting mucosal blood flow compared with prostaglandin E₂. 6 The (15R) methyl epimer administered parenterally had little effect on gastrointestinal function but brief acid incubation greatly increased its activity.