Studies on the pharmacological control of gastric emptying in man

Abstract

Three compounds with differing pharmacological properties have been studied with respect to their effects on gastric emptying, BP, pulse rate and sedation in comparison with placebo in three groups of normal male volunteers. BRL 20627 (10 mg i.v.), a benzamide without dopamine antagonist activity, increased gastric emptying rate (t0.5 BRL 20627 8.3 +/- 0.87 min, placebo 13.8 +/- 2.29 min, P less than 0.005). Zetidoline (20 mg orally), a dopamine D2-receptor antagonist had no significant effect on gastric emptying parameters. BK 34/530 (50 and 100 mg orally) a compound with mixed dopamine agonist and alpha-adrenoceptor antagonist activity, impaired gastric adaptive relaxation as measured by the volume 5 min after the drink and at the higher dose delayed gastric emptying (placebo--5 min volume 256 +/- 44.3 ml, t0.5 15.3 +/- 1.32 min: 50 mg BK 34/530-5 min volume 247 +/- 38 ml, t0.5 14.2 +/- 1.94 min: 100 mg BK 34/530-5 min volume 228 +/- 43.7 ml, t0.5 21.1 +/- 3.82 min). All three drugs resulted in small but significant falls in blood pressure, and in the case of BK 34/530 the 100 mg dose caused significant tachycardia. These studies suggest that dopamine antagonist activity is not a prerequisite for 'gastrokinetic' effects in man, and that there is no inhibitory dopaminergic tone on gastric emptying in normal subjects.