Disease relevance of Prucalopride

• Prucalopride accelerates gastrointestinal and colonic transit in patients with constipation without a rectal evacuation disorder [1].
• The 5-HT(4) selective agonists, prucalopride and renzapride, also increased secreted sAPPalpha in IMR32 human neuroblastoma cells [2].

High impact information on Prucalopride

• This could possibly be achieved with the selective 5-HT4 receptor agonists prucalopride and SDZ HTF-919, which are currently in advanced clinical trials [3].
• Prucalopride did not significantly alter gastric emptying (p>0.5) or small bowel transit (overall p=0. 12) [4].
• METHODS AND RESULTS: Here we show that the subacute intraperitoneal (IP) injection of the 5-HT4 receptor agonists prucalopride (2.5 mg/kg) and RS 67333 (1.5 mg/kg) 30 minutes before the beginning of recordings augment the mean firing rate of DRN neurons by 40% and 66%, respectively [5].
• The 5-HT(4) serotonin receptor agonists cisapride and prucalopride, at concentrations between 10(-10) M and 10(-8) M, reduced interferon-gamma-induced MHC class II immunostaining in cultured astrocytes derived from newborn Wistar rats by approximately 50-60% [6].
• The aims of this study were to investigate the effects of prucalopride on I(CaL), action potentials, refractory period, and arrhythmic activity in human atrial myocytes, and to compare these with the effects of 5-HT, using the whole-cell perforated patch-clamp technique [7].

Chemical compound and disease context of Prucalopride

• The 5-HT4 agonists induce peristalsis; tegaserod and prucalopride, both delayed in their development due to issues of safety and efficacy, benefit patients with 'constipation-predominant' irritable bowel syndrome or idiopathic constipation [8].
• Recently, a new serotonin (5-HT4) receptor agonist prucalopride was shown to have remarkable prokinetic properties, resulting in symptomatic improvement and increased frequency of defecation in patients with chronic functional constipation [9].

Biological context of Prucalopride

• Prucalopride (10 microM) significantly increased the action potential duration at 50% repolarization (APD50) from 12 +/- 2 to 17 +/- 3 ms (p < 0.05; n = 22 cells, 9 patients) [7].
• Despite the deficit in synaptic transmission present in these mice, the percentage increase of the CA1 population spike induced by Prucalopride was the same as that observed in wild-type mice [10].
• As it is intended for treatment of intestinal motility disorders, it is important to note that prucalopride is devoid of anti-cholinergic, anticholinesterase or nonspecific inhibitory activity and does not antagonise 5-HT(2A), 5-HT(2B) and 5-HT(3) receptors or motilin or CCK(1) receptors [11].
• Prucalopride is a gastrointestinal prokinetic drug that acts through 5-HT4 receptors, but its potential effects on cardiac atrial function are unknown [12].

Anatomical context of Prucalopride

• Electrophysiological effects of prucalopride, a novel enterokinetic agent, on isolated atrial myocytes from patients treated with beta-adrenoceptor antagonists [7].
• Regional differences in response to prucalopride were not observed in human ascending and sigmoid colon and rectum [13].
• The prucalopride-induced increase was present in canine ascending and descending colon, but absent in rectum [13].
• We investigated the effects of prucalopride on human right atrium, piglet left atrium, and piglet sinoatrial node [12].
• Efficacy and tolerability of prucalopride in patients with constipation due to spinal cord injury [14].

Associations of Prucalopride with other chemical compounds

• The IC(50) value for prucalopride to block HERG (5.7 10(-6) M) was 20-fold higher than that of cisapride [15].
• In constipation-predominant IBS the colokinetic effects of the selective 5HT4 agonists prucalopride and tegaserod are of great interest [16].

Gene context of Prucalopride

• Hypomotility remains an attractive therapeutic target in IBS and the new generation of prokinetics includes several partial agonists at the 5-HT4 receptor, such as tegaserod (HTF-919) and prucalopride (R0-93877) [17].
• To investigate the potential use of 5-HT(4) agonists in the treatment of AD, Prucalopride was applied to hippocampal slices from a transgenic mouse line that overexpresses the Abeta peptide [10].
• Prucalopride did not cause relevant inhibition of 5-HT(2A), 5-HT(2B), or 5-HT(3), motilin or cholecystokinin (CCK(1)) receptor-mediated contractions, nor nicotinic or muscarinic acetylcholine receptor-mediated contractions, up to 10 microM [11].
• We evaluate the tolerability and pilot efficacy of prucalopride in the treatment of CC due to SCL [14].
• AIMS: Pilot study to compare the efficacy and tolerability of prucalopride and placebo in patients with severe CC referred to a tertiary centre [18].

Analytical, diagnostic and therapeutic context of Prucalopride

• Prucalopride tended to increase the transit after laparotomy with or without mechanical stimulation when given alone [19].
• Effect of prucalopride, a new enterokinetic agent, on gastrointestinal transit and anorectal function in healthy volunteers [20].
• However, further placebo-controlled double blind studies are needed for full documentation of the usefulness of prucalopride in patients with scleroderma [9].
• Prucalopride, notplacebo, increased rectal sensitivity to distension (urge volume, P=0.01) and electrical stimulation (P=0.001) [21].
• METHODS: Twenty-eight patients were enrolled in this double-blind, placebo-controlled, crossover study (prucalopride: 1 mg, n=12; 2 mg, n=16) [22].

References