5-HT₄Receptor Ligands:  Applications and New Prospects

Visceral analgesic effect of 5-HT4 receptor agonist in rats involves the rostroventral medulla (RVM)

“…Microdialysis in the brain has shown an increase in acetylcholine release following intra-cerebroventricular (i.c.v) injection of the 5-HT 4 agonists and this effect can be reduced by co-administration of the 5-HT 4 antagonists (Consolo et al, 1994). Studies have also documented that relatively high expression of 5-HT 4 receptors in the region of the limbic system, hippocampus, basal ganglia and nigrostriatal pathways that play important roles in learning, memory, depression and anxiety (Grossman et al, 1993; Waeber et al, 1993; Jakeman et al, 1994; Doménech et al, 1994; Schiavi et al, 1994; Waeber et al, 1994; Patel et al, 1995; Mengod et al, 1996; Langlois and Fischmeister, 2003). The rostroventral medulla (RVM) forms part of a descending pathway that modulates nociceptive neurotransmission at the level of the dorsal horn.…”

Synthesis and pharmacological properties of novel hydrophilic 5-HT4 receptor antagonists

“…In clinical studies with the 5-HT 4 agonists metoclopramide and cisapride facilitation of urinary bladder emptying and occasional urinary incontinence was observed. 16 The 0968-0896/$ -see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.bmc.2010.…”

“…16 It is therefore possible that 5-HT 4 antagonists which access the CNS would have undesirable side effects.…”

Azaadamantane benzamide 5-HT4 agonists: gastrointestinal prokinetic SC-54750

“…12 An excellent review of the 5-HT 4 receptor and key ligands was recently published. 13 We have investigated a number of conformationally-constrained tertiary amine derivatives as serotonin 5-HT 4 agonist and antagonists, and as 5-HT 3 antagonists. 14 We previously reported the 5-HT 4 activity of pyrrolizidine SC-53116, 15 the first selective 5-HT 4 agonist, and SC-53606, a selective 5-HT 4 antagonist.…”