EFFECT OF LOPERAMIDE ON LOWER ESOPHAGEAL SPHINCTER PRESSURE IN IDIOPATHIC ACHALASIA

Background: We have recently shown that in achalasia patients morphine has a striking inhibitory action on resting lower oesophageal sphinct er (LOS) pressure, which is mediated by opioid receptors. The aim of t his study was to investigate the effect of a peripheral opioid agonist , loperamide, administered at a dose of IG mg, on resting LOS pressure in nine patients with untreated idiopathic achalasia. Methods: All pa tients underwent two experiments after oral administration of placebo and loperamide, respectively, on separate days and in randomized order . At the end of the placebo experiment we also tested the effect of lo peramide as compared with distilled water. both infused intraluminally at the level of the LOS. In the loperamide experiment, after a 60-min basal period, naloxone, 40 mu g/kg, was injected intravenously, and r ecordings continued for a further 10 min. Results: Loperamide administ ered orally decreased (p < 0.01) LOS pressure by la +/- 2 mmHg (37 +/- 7%) compared with placebo, and naloxone intravenously failed to block the effect. LOS pressure was not affected by infusion of either disti lled water or loperamide at the level of the LOS. Conclusions: Our fin dings indicate that in patients with idiopathic achalasia oral adminis tration of loperamide at a high dose markedly decreases resting LOS pr essure. This may not occur through opioid receptor stimulation and req uires intestinal absorption of the drug. The possible effect of combin ing a small dose of loperamide with the traditional achalasia drugs aw aits further evaluation.