Effects of a nonpeptide motilin receptor antagonist on proximal gastric motor function.
OBJECTIVE
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.
Kamerling
Ingrid M C
IM
Centre for Human Drug Research, Leiden, the Netherlands.
van Haarst
Aernout D
AD
Burggraaf
Jacobus
J
Schoemaker
Rik C
RC
de Kam
Marieke L
ML
Heinzerling
Hartmut
H
Cohen
Adam F
AF
Masclee
Ad A M
AA
D000293:Adolescent; D000328:Adult; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D008875:Middle Aged; D009037:Motilin / Q000097:blood / Q000493:pharmacokinetics*; D009046:Motor Neurons / Q000187:drug effects*; D011964:Receptors, Gastrointestinal Hormone / Q000037:antagonists & inhibitors*; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors*; D012677:Sensation; D013270:Stomach / Q000294:innervation*
D011964:Receptors, Gastrointestinal Hormone; D018013:Receptors, Neuropeptide; C050802:motilin receptor; D009037:Motilin