A comparison of the gastric and central nervous system effects of two substituted benzamides in normal volunteers.

Abstract

1 Eight healthy male volunteers participated in a single-blind, random allocation, crossover, comparison of intravenous metoclopramide (10 mg), the peripherally acting, gastrointestinal stimulant BRL 20627 (10 mg) and saline. 2 The central nervous system effects were assessed by quantitative electroencephalography (EEG) and by visual analogue scales. Gastric motility and emptying were assessed by epigastric impedance.3 Metoclopramide increased the EEG amplitude by 10.4% (a statistically significant, P < 0.05, effect) and increased frequencies above 22 Hz, whereas both BRL 20627 and placebo had only minor effect on the EEG frequencies and slightly decreased the EEG amplitude. Ratings on visual analogue scales showed that metoclopramide caused statistically significant (P < 0.01 difference from placebo) restlessness and slight but significantly less (P < 0.05 difference from placebo) feeling of happiness. 4 Epigastic impedance changes indicated that both metoclopramide and BRL 20627 increased gastric contractile activity, but the rate of gastric emptying was not significantly altered by either drug although it tended to be shortened following metoclopramide but not BRL 20627 treatment. 5 It is concluded that since the published animal data show that BRL 20627 has only weak dopamine antagonistic properties this study further implicates dopamine receptor blockade in the akathisia but not in the gastric effect of metoclopramide.

Double‐blind, randomized, placebo‐controlled study to evaluate the effects of tegaserod on gastric motor, sensory and myoelectric function in healthy volunteers

“…It is also conceivable that the lack of effect was due to the exclusive participation of healthy volunteers. There are several studies on prokinetic agents such as cisapride and metoclopramide which do not show acceleration of gastric emptying in healthy individuals 24–28 . We suspect that the lack of change in gastric emptying observed in this healthy volunteer study reflects the fact that it is much harder to alter gastric emptying in health presumably because reflex mechanisms such as duodenal feedback loops can counteract any prokinetic effect of a drug.…”