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ONO-8539 a novel therapeutic option for managing heartburn

12 Oct 2017

The novel prostanoid EP1 receptor antagonist ONO-8539 appears to attenuate acid-induced heartburn in healthy men, suggesting that EP1 receptors play a role in generating heartburn symptoms, according to a study.

A total of 20 males were randomized to receive either ONO-8539 (450 mg) or placebo, administered once 4 hours prior to acid perfusion test, during which hydrochloric acid at 0.15 mol l−1 was perfused into the lower oesophagus for half an hour.

Acid perception threshold was calculated as the time to first sensation of heartburn. Severity of upper gastrointestinal (GI) symptoms was assessed using a validated categorical rating scale. Upper GI symptoms of interest included heartburn, sour or bitter taste, pricking pain in the stomach, dull pain in the stomach, heavy feeling in the stomach, tight feeling in the stomach, nausea, and sensation of fullness.

Results revealed that compared with placebo, ONO-8539 significantly reduced total heartburn symptom score, but not other upper GI symptom scores, during acid perfusion (area under the curve, 56.5 with ONO-8539 vs 85.0 with placebo; p<0.01).

Furthermore, the time to first sensation of heartburn was significantly prolonged with ONO-8539 vs placebo (9.7 vs 4.3 minutes; p<0.05).

The present data show ONO-8539 as a potential novel therapeutic option for controlling heartburn symptoms in patients with gastro-oesophageal reflux disease.

ONO-8539 inhibits the EP1 receptor, which is one of the prostaglandin E2 (PGE2) receptors. In particular, oesophageal PGE2 plays an essential role in the induction and generation of heartburn symptoms in humans. Such mechanism of action of ONO-8539 has been classified as ‘‘insurmountable’’ and ‘‘competitive,’’ characterized by a long duration of inhibitory effect due to slow dissociation from the receptors. [Am J Physiol Gastrointest Liver Physiol 2013;304:G568–73]

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2 days ago
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