Trimebutine

Trimebutine is a multi-target inhibitor and opioid receptor agonist with antimuscarinic activity. Trimebutine inhibits L-type Ca²⁺ channels and large-conductance calcium-activated potassium channels (BK_Ca channels), thereby inhibiting extracellular calcium influx and potassium ion efflux. Trimebutine also targets Toll-like receptors, inhibits Toll-like receptor 2/4/7/8/9 signals, and inhibits LPS-induced IRAK1 activation, as well as ERK1/2, JNK and NF-κB activation, thereby exerting anti-inflammatory effects. Trimebutine also induces tumor cell apoptosis by inhibiting the AKT/ERK pathway. Trimebutine also inhibits excessive contraction of smooth muscle and can be used in the study of gastrointestinal disorders such as irritable bowel syndrome (IBS)^{[1][2][3][4][5][6]}. In Vitro:Trimebutine (0-1000 μM; 48 h) significantly inhibits the viability of SHG44, U251, and U-87 MG glioma cells, with IC₅₀ of 98.28 μM, 128.27 μM, and 204.06 μM, respectively, and has low toxicity to normal HEB cells^[1].
Trimebutine (0-200 μM; 24-72 h) inhibits the migration of U-87 MG cells in a concentration- and time-dependent manner^[1].
Trimebutine (0-200 μM; 48-72 h) induces apoptosis in glioma cells, downregulates Bcl-2, upregulates Bax and activates Caspase-3, while inhibiting the phosphorylation of AKT (Ser473) and ERK (Thr202/Tyr204)^[1]. In Vivo:Trimebutine (100 mg/kg/day; intraperitoneal injection; once a day; 7 days) inhibits tumor growth in the subcutaneous xenograft model of U-87 MG glioma in female nude mice, increases TUNEL-positive apoptotic cells in tumor tissues, downregulates Bcl-2, upregulated Bax, and inhibits p-AKT and p-ERK signaling pathways^[1].
Trimebutine (50 mg/kg; oral; single dose) significantly reduces pain response at 60 mmHg pressure in the colorectal distension model of male mice after 4 hours of treatment, exhibits weaker overall effect than GIC-1001 (HY-B0380B) at an equimolar dose^[2].