Velusetrag

Velusetrag (TD-5108) is an orally active, potent and selective agonist of serotonin 5-HT₄ receptor (5-HT4R), with a pK_i of 7.7. Velusetrag exhibits no affinity (K_i>10 μM) for 5-HT_2A and 5-HT_2B receptors. Velusetrag can be used for the research of gastrointestinal diseases and Parkinson's disease^{[1][2][3][4][5]}. IC50 & Target: pKi: 7.7 (5-HT4R)^[1][2][3] 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^[1].
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^[1].
Velusetrag (0.001-10 μM) produces a concentration-dependent relaxation of the carbachol (3 μM)-precontracted rat esophagus, with a pEC₅₀ of 7.9^[1]. In Vivo: Velusetrag (3 mg/kg; a single i.p.) significantly improves the facilitation of contextual fear extinction in PD mice^[3].
Velusetrag (3 mg/kg; a single i.p.) increases hippocampal cAMP levels in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice^[3].
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].