EM574, an erythromycin derivative, is a motilin receptor agonist in the rabbit

Abstract This study was performed to examine whether an erythromycin derivative, de( N -methyl)- N -isopropyl-8,9-anhydroerythromycin A 6,9-hemiacetal (EM574) is a motilin receptor agonist in the rabbit gastrointestinal tract. EM574 and porcine motilin induced contractions in segments of isolated rabbit intestine with pEC 50 values of 8.26±0.04 and 8.69±0.07, respectively, but not in rat or guinea pig preparations. The sensitivity and efficacy of the response to both compounds in rabbits decreased aborally and was insensitive to pretreatment with atropine or tetrodotoxin, but was markedly suppressed under Ca 2+ -free conditions. EM574 and porcine motilin specifically displaced [ 125 I-Tyr 23 ]canine motilin bound to gastric antral smooth muscle homogenates with pIC 50 values of 8.21±0.13 and 9.20±0.11, respectively. The pEC 50 value for the contractile response and pIC 50 value for the receptor binding for motilin, EM574, erythromycin A and three other derivatives correlated well ( r =0.94, P