IngentaConnect Effects of a nonpeptide motilin receptor antagonist on proximal g...

Authors: Kamerling I.M.C.¹; van Haarst A.D.¹; Burggraaf J.¹; Schoemaker R.C.¹; de Kam M.L.¹; Heinzerling H.²; Cohen A.F.¹; Masclee A.A.M.³

Source: British Journal of Clinical Pharmacology, Volume 57, Number 4, April 2004 , pp. 393-401(9)

Publisher: Blackwell Publishing

Abstract:

Aim

To assess the effects of the motilin receptor antagonist RWJ-68023 on basal and motilin-stimulated proximal gastric volume. Methods

Eighteen healthy male volunteers received RWJ-68023 in two different doses or placebo for 135 min. After 45 min, subjects received a motilin infusion for 90 min. Proximal gastric volume was measured with a barostat at constant pressure and during isobaric distensions. Abdominal symptoms were scored using visual analogue scales. Motilin and RWJ-68023 concentrations were assessed by radioimmunoassay and liquid chromatography-mass spectrometry, respectively. Results

Both dosages of RWJ-68023 were safe and well tolerated. The most common adverse events were of gastrointestinal origin. RWJ-68023 did not affect basal proximal gastric volume, but the high-dose RWJ-68023 reduced the contractile effect of motilin on the stomach. This antagonizing effect of RWJ-68023 was only significant (P = 0.014) during the distension procedure. Conclusions

The RWJ-68023 doses used in this study were selected to accomplish plasma concentrations that would block the motilin effect entirely. However, the antagonizing effect of RWJ-68023 was partial and only present when the tonic condition of the stomach was modulated by motilin.

Keywords: antagonist; human and barostat; motilin; stomach

Document Type: Research article

DOI: 10.1046/j.1365-2125.2003.02034.x

Affiliations: 1: Centre for Human Drug Research, Leiden, the Netherlands, 2: Johnson & Johnson Pharmaceutical Research and Development, Janssen-Cilag, High Wycombe, UK, and 3: Leiden University Medical Centre, Department of Gastroenterology, Leiden, the Netherlands

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Effects of a nonpeptide motilin receptor antagonist on proximal gastric motor function