EM574, an erythromycin derivative, improves delayed gastric emptying of semi-solid meals in conscious dogs

The gastroprokinetic effects of de( N-methyl)-N-isopropyl-8,9-anhydroerythr omycin A 6,9-hemiacetal (EM574), a non-peptide motilin receptor agonist, we re investigated in conscious dogs in a normal state and with experimentally -induced gastroparesis. Gastric emptying of semi-solid meals was assessed i ndirectly from acetaminophen absorption with simultaneous recording of gast ric antral motility. In the normal state, post-prandial intraduodenal admin istration of EM574 (30 mg/kg) stimulated antral motility and significantly enhanced gastric emptying as potently as did intravenous porcine motilin (0 .003 mg/kg/h). Intraduodenal cisapride at 1 mg/kg denal cisapride at 1 mg/k g elicited antral contractions and tended to accelerate gastric emptying bu t at 3 mg/kg, gastric emptying was not enhanced despite a further increase in the motor index. In dogs with gastroparesis induced by intraduodenal ole ic acid or intravenous dopamine, EM574 (0.03 mg/kg) increased antral motili ty and reversed the delayed gastric emptying completely. Cisapride (1 mg/kg ) partially ameliorated the impaired emptying under these conditions. In at ropinized dogs, no acceleration of gastric emptying by EM574 was observed. These results indicate that EM574 potently accelerates gastric emptying of caloric meals in dogs in a normal state and with experimentally-induced gas troparesis, and also suggest that the effect is mediated through stimulatio n of a cholinergic neural pathway. (C) 2000 Elsevier Science B.V. All right s reserved.