RQ-00201894: A motilin receptor agonist causing long-lasting facilitation of human gastric cholinergically-mediated contractions

The aim was to characterise rq-00201894,a novel non-macrolide motilin agonist,using human recombinant receptors and then investigate its ability to facilitate cholinergic activity in human stomach. a reporter gene assay assessed motilin receptor function. selectivity of action was determined using a panel of different receptors,ion channels,transporters and enzymes. cholinergically-mediated muscle contractions were evoked by electrical field stimulation (efs) of human gastric antrum. the results showed that rq-00201894,motilin and erythromycin acted as full motilin receptor agonists (ec50: 0.20,0.11,69 nm,respectively). in this function,rq-00201894 had >90-fold selectivity of action over its ability to activate the human ghrelin receptor (ec50 19 nm) and greater selectivity over all other receptors/mechanisms tested. in human stomach rq-00201894 0.1-30 μm concentration-dependently increased efs-evoked contractions (up to 1209%; pec50 6.0). at 0.1-10 μm this activity was usually prolonged. at higher concentrations (3-30 μm) rq-00201894 also caused a short-lasting muscle contraction,temporally disconnected from the increase in efs-evoked contractions. rq-00201894 10 μm did not consistently affect submaximal contractions evoked by carbachol. in conclusion,rq-00201894 potently and selectively activates the motilin receptor and causes long-lasting facilitation of cholinergic activity in human stomach,an activity thought to correlate with an ability to increase gastric emptying. © 2015 japanese pharmacological society.