Treatment functional GI disease: the complex pharmacology of serotonergic drugs

摘要: We have read the recent review [1] on use of serotonergic drugs in functional gut disorders with great interest and would like to comment two aspects that may confuse readers involved drug development this difficult area. First, Dr Spiller states prolongation QT interval by cisapride is due an action cardiac 5-HT4 receptors. However, there now consensus occurrence ventricular tachyarrhythmias such as torsades de pointes blockade human ether-a-go-go-related gene K+ channels [2–5]. Cisapride indeed trigger tachycardia supraventricular arrhythmia through stimulation atrial receptors [6]. incidence very low [7], probably because behaves a partial agonist atrium density [8]. The lack involvement generating also supported failure selective receptor antagonist {"type":"entrez-nucleotide","attrs":{"text":"GR113808","term_id":"238362519","term_text":"GR113808"}}GR113808 [9] modify cisapride-induced potential guinea-pig isolated papillary muscles. Thus, we conclude not class effect necessarily shared all agonists it possible develop no interval: tegaserod be example [10]. In addition, should noticed so far developed (including cisapride, prucalopride tegaserod) are agonists, but only presented Table 1 Spiller's paper. Secondly, point out buspirone sumatriptan both defined 5-HT1P throughout review, whereas 5-HT1A (and dopamine D2 antagonist) [11] prototype 5-HT1B/D [12]. Sumatriptan has been extensively investigated Tack's group [13, 14] was found important effects gastric tone perception distension [14], mediating its still matter debate. Therefore, fact therapeutic targets misleading, more included official IUPHAR classification serotonin [12]. We aware presence reported enteric neurones [15], hypothesis determines motor vivo these awaits confirmation pharmacological studies antagonists. It noteworthy, however, preliminary report our [16] showed blocked {"type":"entrez-nucleotide","attrs":{"text":"GR127935","term_id":"238377770","term_text":"GR127935"}}GR127935, antagonist.