Effects of the enterokinetic prucalopride (R093877) on colonic motility in fasted dogs.

The novel enterokinetic drug prucalopride was tested at various intravenous and oral doses in fasted dogs to assess: (i) the effects on colonic contractile motility patterns; and (ii) the mediation of these effects by 5-hydroxytryptamine (5-HT4) receptors. Colonic motility patterns were assessed in conscious dogs with four chronically implanted strain-gauge force transducers that were sutured on the serosal side of the colon. Prucalopride altered colonic contractile motility patterns in a dose-dependent fashion by stimulating high-amplitude clustered contractions in the proximal colon and by inhibiting contractile activity in the distal colon.

The in vitro pharmacological profile of prucalopride, a novel enterokinetic compound.

Prucalopride is a novel enterokinetic compound and is the first representative of the benzofuran class. We set out to establish its pharmacological profile in various receptor binding and organ bath experiments. Receptor binding data have demonstrated prucalopride's high affinity to both investigated 5-HT(4) receptor isoforms, with mean pK(i) estimates of 8.

An improved in vitro bioassay for the study of 5-HT(4) receptors in the human isolated large intestinal circular muscle.

Recently, it was demonstrated that 5-HT induces relaxation of human colon circular muscle through activation of 5-HT(4) receptors and 5-HT(7) receptors. The aim of the current study was to develop a new in vitro bioassay of human colon that would facilitate the pharmacological analysis of 5-HT responses mediated solely by 5-HT(4) receptors. Contracting circular muscle strips with KCl (80 mM) yielded a stable contractile tension and, in contrast to muscarinic cholinoceptor agonists and histamine, a profound reduction of spontaneous contractility.

Evidence for 5-HT7 receptors mediating relaxation of human colonic circular smooth muscle.

5-HT4 receptors mediate relaxation of human colon circular muscle. However, after 5-HT4 receptor blockade (SB 204070 10 nM), 5-HT still induced a relaxation (pEC50 6.3).