MA-2029

MA-2029 is a selective, orally active, and competitive motilin receptor antagonist (IC₅₀=4.9 nM). MA-2029 is selective for the motilin receptor over various other receptors and ion channels. MA-2029 may be useful for gastrointestinal disorders associated with disturbed gastrointestinal motility^[1]. IC50 & Target: IC50: 4.9 nM (motilin receptor)^[1] In Vitro: MA-2029 (1 to 30 nM) competitively inhibits motilin-induced contractions in isolated rabbit duodenal longitudinal muscle strips, with a pA₂ value of 9.17±0.01. Contractile responses to acetylcholine and substance P are unaffected even at 1 μM of MA-2029. MA-2029 concentration-dependently inhibits the binding of [¹²⁵I]motilin to motilin receptors in a homogenate of rabbit colon smooth muscle tissue and membranes of HEK 293 cells expressing human motilin receptors. The pK_i of MA-2029 is 8.58±0.04 in the rabbit colon homogenate and 8.39 in the HEK 293 cells^[1]. In Vivo: MA-2029 (0.3-3 mg/kg; p.o.) dose-dependently inhibits the number of abdominal muscle contractions induced under the same conditions and causes significant inhibition at 3 mg/kg^[1].
MA-2029 (10 mg/kg; p.o.) treatment shows that the t_1/2 is 2 hours^[1].
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 administration of 10 mg/kg or more causes inhibitory effects from 30 min or less to at least 4 h after administration^[1].