952 ONO-8539, a Novel Prostanoid EP1 Receptor Antagonist, Suppresses Transient Lower Esophageal Sphincter Relaxations in Monkeys

Konemura, Takashi; Date, Ichiro; Okada, Hiroki

doi:10.1016/s0016-5085(14)60594-1

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“…In the present study, ONO-8539 significantly reduced the number of TLESRs by 20% without affecting many manometric parameters including basal LES pressure, in healthy male subjects, similar to an animal study [20]. ONO-8539 might affect the brainstem or afferent nerves in the vagovagal pathway because the medulla oblongata and nodose ganglion expressed the EP1 receptor more than did the lower esophageal mucosa and muscle in monkeys [20]. However, the distribution of EP1 receptors in the human esophagus remains unclear.…”

Section: Discussion/conclusionsupporting

confidence: 85%

“…Although the previous study reported that celecoxib, cyclooxygenase-2 inhibitor, increased canine LES pressure, little is known about the effect of PGE2 system on the human esophageal LES [19]. A recent study found that an EP1 receptor antagonist, ONO-8539, significantly inhibited TLESRs in monkeys without altering the basal LES pressure, possibly by acting on the vago-vagal reflex pathway [20]. However, the effect of EP1 receptor antagonist on TLESRs in humans remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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Effect of EP1 Receptor Antagonist on Transient Lower Esophageal Sphincter Relaxations in Humans

et al. 2019

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Background/Aims: Transient lower esophageal sphincter relaxations (TLESRs) are the major cause of gastroesophageal reflux. Recently, an EP1 receptor antagonist, ONO-8539, showed the reduction of TLESRs in monkeys. However, its effect on TLESRs in humans remains unclear. This study investigated the effect of ONO-8539 on postprandial TLESRs in healthy male subjects. Methods: Twenty-seven subjects participated in this placebo-controlled, cross-over study. The subjects received either placebo or ONO-8539 (450 mg) after a standardized breakfast. A 30-min basal recording was performed 4 h after drug administration. Subsequently, TLESR recordings were performed after a high-fat test meal for 3 h. The examination was repeated at least 7 days from the first evaluation for washout. Results: Thirteen patients were ultimately analyzed. The basal lower esophageal sphincter pressure was not different between the 2 groups (16.3 and 18.0 mm Hg for placebo and ONO-8539, respectively; p = 0.88). ONO-8539 significantly reduced the number of TLESRs from 15.0 to 12.0 for 3 h (p < 0.05). The proportion of terminating events of TLESRs was significantly different between the 2 groups (p < 0.05). No events and swallowing terminated more TLESRs with ONO-8539 than with placebo. Conclusions: ONO-8539 suppressed TLESRs mildly. EP1 receptor may be involved with the mechanism of human TLESRs.

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Section: Discussion/conclusionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%