Effect of loperamide on lower oesophageal sphincter pressure in idiopathic achalasia

We have recently shown that in achalasia patients morphine has a striking inhibitory action on resting lower oesophageal sphincter (LOS) pressure, which is mediated by opioid receptors. The aim of this study was to investigate the effect of a peripheral opioid agonist, loperamide, administered at a dose of 16 mg, on resting LOS pressure in nine patients with untreated idiopathic achalasia.

All patients 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 loperamide 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 micrograms/kg, was injected intravenously, and recordings continued for a further 10 min.

Loperamide administered orally decreased (p < 0.01) LOS pressure by 10 +/- 2 mmHg (37 +/- 7%) compared with placebo, and naloxone intravenously failed to block the effect. LOS pressure was not affected by infusion of either distilled water or loperamide at the level of the LOS.

Our findings indicate that in patients with idiopathic achalasia oral administration of loperamide at a high dose markedly decreases resting LOS pressure. This may not occur through opioid receptor stimulation and requires intestinal absorption of the drug. The possible effect of combining a small dose of loperamide with the traditional achalasia drugs awaits further evaluation.