Effects of LY267108, an erythromycin analogue derivative, on lower esophageal sphincter function in the cat

  • Gastroenterology. 1994 Mar;106(3):624-8. doi: 10.1016/0016-5085(94)90694-7.
B Greenwood  1 ,  D Dieckman ,  H A Kirst ,  J S Gidda
Affiliations
  • 1. Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana.
PMID: 8119532 DOI: 10.1016/0016-5085(94)90694-7
Abstract

Background/aims: Erythromycin (EM-A) and some of its analogues stimulate gastrointestinal smooth muscle contractions. Because gastroesophageal reflux disease (GERD) in humans is in part caused by a reduction in lower esophageal sphincter (LES) pressure, the aim of this study was to investigate the effect of LY267108 (an EM-A analogue with no significant antimicrobial activity) on LES function.

Methods: In ketamine-anesthetized cats, LES pressure was recorded using a Dent sleeve.

Results: In cats, LY267108 increased LES pressure, as did motilin and EM-A. Neither LY267108, EM-A, nor motilin altered LES relaxation in response to a swallow. LY267108 increased LES pressure in cats in which the basal LES pressure was lowered experimentally by perfusing the distal esophagus with HCl (0.1 N for 3 days) or following isoproterenol (3.0 micrograms/kg intravenously). In summary, LY267108 increases LES pressure in normal cats, did not affect the relaxation of the LES in response to a swallow, and increases LES pressure in Animals with an experimentally induced decrease in LES pressure.

Conclusions: The results suggest that LY267108 may be useful in treating GERD because of its ability to increase LES pressure and thus present a barrier for gastroesophageal reflux.

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