ASP 7663

ASP7663 is an orally active and selective TRPA1 agonist. ASP7663 exerts both anti-constipation and anti-abdominal pain actions[1][2].

Signaling Pathways >> Membrane Transporter/Ion Channel >> TRP Channel

Research Areas >> Neurological Disease

ASP7663 concentration dependently increases intracellular Ca2+ concentration in human, rat, and mouse TRPA1 expressed in HEK293 cells in a similar manner, with respective EC50 values (95% confidence interval [CI]) of 0.51 (0.40–0.66), 0.54 (0.41–0.72), and 0.50 (0.41–0.63) μmol/L[1]. ASP7663 concentration-dependently stimulates 5-HT release from QGP-1 cells, a lineage of TRPA1-expressing EC cells, with an EC50 value of 72.5 (52.6–99.9) μmol/L[1].

ASP7663 significantly improves the loperamide-induced delay in colonic transit in mice[1]. ASP7663 (orally, 0.3 and 1 mg/kg) significantly shortens the prolonged bead expulsion time caused by loperamide[1]. ASP7663 (orally, 1 and 3 mg/kg) exhibits inhibitory effects on colorectal distension in rat[1]. Animal Model: CRD model (colorectal distension in rat)[1]. Dosage: 1 and 3 mg/kg. Administration: Orally. Result: Significantly reduced the number of abdominal contractions evoked during CRD at pressures of 30, 45, and 60 mmHg. ASP7663 also reduced the number of abdominal contractions by intravenous treatment.

[1]. Ryosuke Kojima, et al. Effects of Novel TRPA1 Receptor Agonist ASP7663 in Models of Drug-Induced Constipation and Visceral Pain. Eur J Pharmacol. 2014 Jan 15;723:288-93.

[2]. Yao Lu, et al. Transient Receptor Potential Ankyrin 1 Activation Within the Cardiac Myocyte Limits Ischemia-reperfusion Injury in Rodents. Anesthesiology. 2016 Dec;125(6):1171-1180.