EM-523, an erythromycin derivative, and motilin show similar contractile activity in isolated rabbit intestine.
The effect of EM-523 [de(N-methyl)-N-ethyl-8,9-anhydroerythromycin A 6,9-hemiacetal], an erythromycin derivative, on preparations of isolated intestine of rabbits, rats and guinea pigs was investigated and compared to the effects of motilin and prostaglandin F2 alpha (PGF2 alpha). EM-523 and motilin induced contractions in the rabbit intestinal preparations but not in the rat or guinea pig preparations. In contrast, PGF2 alpha induced contractions in all three intestinal preparations. The rabbit duodenum and jejunum were more sensitive than the ileum to EM-523 and motilin, but no selectivity was observed with PGF2 alpha. The contractile responses induced by EM-523 and by motilin were not influenced by pretreatment with tetrodotoxin, atropine, naloxone or mepyramine but were greatly suppressed by pretreatment with verapamil or removal of calcium ions from the medium, suggesting that both agents induce intestinal contractions by acting directly on smooth muscle and that their actions depend largely on extracellular calcium. The contractile response to EM-523 or motilin was reduced markedly after treatment of the preparation with a high concentration of either agent, and cross-tachyphylaxis between EM-523 and motilin was also observed. These findings indicate that the contractile activity of EM-523 is very similar to that of motilin and that EM-523 and motilin may share the same site of action.
Satoh
T
T
Research Department, Shimizu Pharmaceutical Co., Ltd., Shizuoka, Japan.
Inatomi
N
N
Satoh
H
H
Marui
S
S
Itoh
Z
Z
Omura
S
S
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology; D004347:Drug Interactions; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D007421:Intestine, Small / Q000187:drug effects; D008297:Male; D009037:Motilin / Q000494:pharmacology*; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000187:drug effects*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013779:Tetrodotoxin / Q000494:pharmacology
D013779:Tetrodotoxin; D009037:Motilin; D004917:Erythromycin; D001285:Atropine; D015237:Dinoprost; C061752:EM 523; D000109:Acetylcholine