pKi: 8.8
RS 67506 hydrochloride is a potent and selective 5-HT4 partial agonist.
Selective agonists of 5-HT4 receptor can not only enhance congnitive performance, facilitate gastrointestinal motility, and also correct micturation disturbances which is associated with detrusor hypomotilityor actas analgesics.
In vitro: RS 67506 acted as a potent partial agonist with respect to 5-HT at the 5-HT4 receptor regulating relaxation of the carbachol-precontracted oesophagus. Relaxant responses to RS 67506 was surmountably antagonized with apparent affinities (pKB) of 9.0. RS 67506, therefore, acted as potent, partial 5-HT4 receptor agonists in vitro. The compound may have been used in elucidating the physiological role in 5-HT4 receptors by virtue of their high potency and selectivity [1].
In vivo: RS 67506 induced dose-dependent potentiates heart rate of the anaesthetized micropig (ED50 5.4 pg kg-1, i.v.) with maximal increases of 47 beats min-1 [1]. In addition, in a rat model of spatial learning and memory, the effects of two novel potent and selective 5-HT4 receptor agonists (RS67333 and RS67506) were studied. By contrast, there was no effect seen to RS67506 (0.1, 10 and 1000 pg/kg, i.p.) of equivalent potency and selectivity to RS67333.This differential result may suggest the enhanced ability of RS67333 to enter the CNS, with respect to RS67506 [2].
Clinical trial: So far, no clinical study has been conducted.
References:
[1]. Eglen RM, Bonhaus DW, Johnson LG, Leung E, Clark RD. Pharmacological characterization of two novel and potent 5-HT4 receptor agonists, RS 67333 and RS 67506, in vitro and in vivo. Br J Pharmacol. 1995 Aug;115(8):1387-92.
[2]. Fontana DJ, Daniels SE, Wong EH, Clark RD, Eglen RM. The effects of novel, selective 5-hydroxytryptamine (5-HT) 4 receptor ligands in rat spatial navigation. Neuropharmacology. 1997 Apr-May;36(4-5):689-96.