Velusetrag (TD-5108) hydrochloride is an orally active, potent and selective agonist of serotonin 5-HT4 receptor (5-HT4R), with a pKi of 7.7. Velusetrag hydrochloride exhibits no affinity (Ki>10 μM) for 5-HT2A and 5-HT2B receptors. Velusetrag hydrochloride can be used for the research of gastrointestinal diseases and Parkinson’s disease[2].In Vitro: Velusetrag (10 pM-100 μM) concentration-dependently increases the cAMP in HEK-293 cells stably transfected with the h5-HT4(c) receptor, with a pEC50 of 8.3.
Velusetrag (100 pM-1 μM) produces concentration-dependent contraction of the guinea pig colonic longitudinal muscle/myenteric plexus (LMMP), with a pEC50 of 7.9.
TD-5108 (0.001-10 μM) produces a concentration-dependent relaxation of the carbachol (3 μM)-precontracted rat esophagus, with a pEC50 of 7.9.In Vivo: Velusetrag (3 mg/kg; a single i.p.) significantly improves the facilitation of contextual fear extinction in PD mice.
Velusetrag (3 mg/kg; a single i.p.) increase hippocampal cAMP levels in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice.
Velusetrag (0.003-3 mg/kg; a single s.c.) increases colonic transit in a dose-dependent manner and reduces the time taken for excretion of the dye in guinea pigs[2].
Velusetrag (0.003-1 mg/kg; a single i.v.) dose-dependently increases inter-crystal distance, consistent with relaxation of the oesophagus in rats[2].