A double-blind dose ranging study of BRL 24924 and metoclopramide on lower oesophageal sphincter pressure in healthy volunteers.

1. A double-blind placebo controlled dose ranging study of the effect of single oral doses of 1 and 2 mg BRL 24924 and 10 mg metoclopramide on lower oesophageal sphincter pressure has been performed in 20 healthy volunteers. 2. The 2 mg dose of BRL 24924 caused a statistically significant increase in mean lower oesophageal sphincter pressure (P less than 0.05) at 30-45 min post-dose (20.8 +/- 7.1 cm H2O BRL 24924; 16.4 +/- 5.7 cm H2O placebo). BRL 24924 1 mg and metoclopramide 10 mg failed to increase lower oesophageal sphincter pressure at any time. However, eight volunteers with a hypotensive resting lower oesophageal sphincter pressure (less than 15 cm H2O) showed a statistically significant rise in pressure at 120 min for both 1 mg, 2 mg (P less than 0.01; P less than 0.001) BRL 24924 and 10 mg metoclopramide (P less than 0.01). No other significant effect was detected on oesophageal manometry. 3. BRL 24924 (2 mg) has statistically significant effects on lower oesophageal sphincter pressure. However, further studies in patients with gastro-oesophageal reflux disease and oesophagitis are needed to evaluate its clinical efficacy, especially where a hypotensive lower oesophageal sphincter pressure predominates.