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.
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.