MA-2029 is selective for the motilin receptor over various other receptors and ion channels. MA-2029 is a selective and competitive motilin receptor antagonist (IC50=4.9 nM). MA-2029 may be useful for gastrointestinal disorders associated with disturbed gastrointestinal motility.

Motilin receptor:4.9 nM

MA-2029 exhibits a concentration-dependent inhibition of [125I]motilin binding to motilin receptors both in rabbit colon smooth muscle tissue homogenate and in HEK 293 cell membranes expressing human motilin receptors, demonstrating its specificity. The compound's inhibitory potency (pKi) is recorded at 8.58±0.04 in rabbit colon homogenate and 8.39 in HEK 293 cells. Furthermore, in isolated rabbit duodenal longitudinal muscle strips, MA-2029 (1 to 30 nM) competitively inhibits motilin-induced contractions, achieving a pA2 value of 9.17±0.01, indicating significant antagonistic activity. Notably, even at concentrations up to 1 μM, MA-2029 does not affect the contractile responses induced by acetylcholine and substance P, underscoring its selective action on motilin-mediated pathways.

MA-2029 (10 mg/kg; p.o.) treatment displays that the t1/2 is 2 hours. The inhibition is significant at 30 min after administration of 3 mg/kg or more and at 4 h after administration of 10 mg/kg or more (MA-2029), so the administration of 10 mg/kg or more causes inhibitory effects from 30 min or less to at least 4 h after administration. MA-2029 (0.3-3 mg/kg; p.o.) dose-dependently suppresses the number of abdominal muscle contractions induced under the same conditions and cause significant inhibition at 3 mg/kg .