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].

Research Areas >> Others

Signaling Pathways >> GPCR/G Protein >> Motilin Receptor

IC50: 4.9 nM (motilin receptor)[1]

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 pKi of MA-2029 is 8.58±0.04 in the rabbit colon homogenate and 8.39 in the HEK 293 cells[1].

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 t1/2 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]. Animal Model: Male Japanese-white rabbits (about 2-3 kg)[1] Dosage: 0.3, 1, 3 mg/kg Administration: Oral administration Result: Dose-dependently inhibited the number of abdominal muscle contractions induced under the same conditions. Caused significant inhibition at 3 mg/kg. Animal Model: Male Japanese-white rabbits (about 2-3 kg)[1] Dosage: 10 mg/kg Administration: Oral administration (Pharmacokinetic Analysis) Result: The t1/2 is 2 hours.

[1]. Sudo H, et al. Oral administration of MA-2029, a novel selective and competitive motilin receptor antagonist, inhibits motilin-induced intestinal contractions and visceral pain in rabbits. Eur J Pharmacol. 2008 Mar 10;581(3):296-305.