GR125487

GR125487 (1 mg/kg; s.c.) blocks 5-HT4 receptor agonist (1 mg/kg; p.o.)-induced cognitive enhancement in the novel object recognition task in Wistar rats, whereas GR125487 administered alone does not exhibit the same cognitive enhancement effect; in frontal cortex microdialysis, GR125487 (1 mg/kg, s.c.) also blocks the effect of 5-HT4 receptor agonist (3 mg/kg, p.o.)-induced acetylcholine elevation to approximately 200% of baseline^[4].
GR125487 antagonizes the maximal-dose-induced duodenal and jejunal prokinetic effects of ML10302 (HY-14441) and SR59768 (HY-14441) at a dose that itself has no significant effect in 5 fasted conscious dogs, supporting the involvement of 5-HT4 receptor in the intestinal prokinetic effects of both compounds^[7].
GR125487 (0.3 mg/kg; i.p.; 30 min before Cisplatin (HY-17394)) alone does not significantly inhibit 50 mg/kg Cisplatin-induced emesis in Suncus murinus, but its combination with Granisetron (HY-B0071) (30 mg/kg; p.o.) reduces the number of emetic episodes by approximately 72%; combination with Tropisetron (HY-B0072) does not further enhance the inhibitory effect of Tropisetron, supporting that high-dose Cisplatin-induced emesis involves both 5-HT3 and 5-HT4 receptor^[8].
GR125487 sulfamate (1 mg/kg, s.c.; 30 min before morphine) restores the morphine (10 mg/kg, s.c.)-induced decrease in minute ventilation in mice with chronic neuropathic pain induced by nerve ligation, while showing no significant effect on the decrease in respiratory rate or the increase in tidal volume, supporting the involvement of enhanced brainstem 5-HT4a receptor system in the attenuation of morphine-induced respiratory depression under chronic pain conditions^[9].
GR125487 sulfamate (1 mg/kg/day; s.c. osmotic minipump; 28 days) blocks Fluoxetine (HY-B0102)-induced anxiolytic-like/antidepressant-like behavioral effects in the Corticosterone (HY-B1618) mouse model, including behavioral endpoints such as EPM, splash, tail-suspension, and novelty-suppressed feeding, indicating that 5-HT4 receptor activation is a critical component of these Fluoxetine behavioral effects^[10].
GR125487 sulfamate (1 mg/kg/day; s.c. osmotic minipump; 28 days) partially blocks Fluoxetine-induced increases in Ki-67-positive neural precursors in the hippocampal dentate gyrus and partially blocks DCX-positive newborn neuron maturation-related changes^[10].
GR125487 sulfamate (1 mg/kg/day; s.c. osmotic minipump; 28 days) abolishes Fluoxetine-induced increases in dendritic complexity of DCX-positive newborn granule cells, including increased dendritic length and branch intersections^[10].
GR125487 sulfamate (1, 3 mg/kg; i.p.; 30 min before Fluvoxamine) blocks the inhibitory effect of Fluvoxamine (30 mg/kg, i.p.) on isolation-induced hyperactivity in isolated mice, supporting the involvement of 5-HT4 receptor in the behavioral effects of Fluvoxamine^[11].
GR125487 sulfamate (3 mg/kg, i.p.; administered 30 min before venlafaxine) alone does not block the effect of venlafaxine (HY-B0196) (30 mg/kg; i.p.) in reducing contact-induced hyperactivity, but co-administration with the α2-adrenoceptor antagonist Idazoxan (HY-14561) (0.3 mg/kg) blocks this effect, suggesting that both α2-adrenoceptor and 5-HT4 receptor are involved^[11].
GR125487 sulfamate (1 mg/kg; i.p.; once daily; from 3 days before MPTP (HY-W114750) to day 8) prolongs gastrointestinal transit time and aggravates motor bradykinesia in MPTP-induced Parkinson's disease mice^[12].
GR125487 sulfamate (1 mg/kg, i.p.; once daily; from 3 days before MPTP to day 8) aggravates MPTP-induced dopaminergic neuronal loss and decreases striatal p-JAK2/JAK2, p-PKA, and p-CREB/CREB, supporting its effect on dopaminergic neuronal survival through inhibition of JAK2/PKA/CREB signaling^[12].
GR125487 sulfamate (1 mg/kg, i.p.; once daily; from 3 days before MPTP to day 8) alters the gut microbiota composition in MPTP mice, increases the abundance of bacteria such as Clostridium clostridioforme and Akkermansia muciniphila, and decreases the abundance of bacteria such as Parabacteroides distasonis and Bacteroides fragilis, supporting that the 5-HT4 receptor regulates PD-related neuroinflammation and neurodegenerative processes via gastrointestinal motility/microbiota-gut-brain axis^[12].
GR125487 sulfamate (2.5 mg/kg, i.p.; 30 min before Vanillin (HY-N0098) 400 mg/kg) does not significantly reverse the inhibitory effect of Vanillin on seizure-induced mortality in audiogenic seizure-induced mortality in DBA/1 mice, suggesting that the protective effect of Vanillin is not primarily dependent on 5-HT4 receptor^[13].

GR125487 sulfamate (1 mg/kg, i.p.; once daily; from 3 days before MPTP to day 8) increases GFAP-positive astrocytes by approximately 45.8% in MPTP mice and further increases striatal TNF-α and IL-1β by approximately 30.2% and 17.6%, respectively, while IL-6 remains unchanged, thereby enhancing neuroinflammation^[12].