RS 23597-190 is a high affinity 5-HT4-selective antagonist with in vitro and in vivo efficacy. RS 23597-190 is a 4-amino-5-chloro-2-methoxybenzoate that antagonizes 5-HT-mediated relaxation of carbachol-contracted rat oesphageal muscularis mucosae ex vivo (pA2 = 7.5) and prevents 5-HT-induced tachycardia (tachyarrhythmia) of anaesthetized micropigs in vivo (6 mg/kg RS 23597-190 and 3-10 μ/kg 5-HT via i.v.) by targeting 5-HT4 with high affinity (pKB = 7.8) and selectivity, while exhibiting no efficacy against 5-methoxytryptamine-mediated 5-HT3 activation in guinea-pig ileum and displaying much reduced or little affinity toward 5-HT3 (pKi = 5.7/mouse NG108-15 cells and pKB <5/guinea-pig ileum), dopamine receptors (pKi <4/D1 & <3/D2), muscarinic receptors (pKi <4.5 toward M1/2/3/4), 5-HT1A & 5-HT2 (pKi <5.2).
