L-732138

148451-96-1

C22H18F6N2O3

10 mM in DMSO

Neuronal Signaling, GPCR/G Protein

L-732138 is a selective, potent and competitive neurokinin-1 (NK-1) receptor antagonist with an IC₅₀ of 2.3 nM. L-732138 has 200-fold more potent in cloned human NK-1 receptors than cloned rat NK-1 receptors, and has > 1000-fold more potent than human NK-2 and NK-3 receptors. L-732138 can reduce hyperalgesia and has antitumor action^[1][2].
In Vitro: L-732138 (0 -100 uM; first doubling time; COLO 858, MEL HO and COLO 679 cells) treatment results in a concentration-dependent cytotoxicity. L-732138 inhibits cell growth with IC₅₀ of 44.6 uM for COLO 858 cells, 76.3 uM for MEL HO cells and 64.2 uM for COLO 679 cells. L-732138 blocks substance P (SP) mitogen stimulation^[1].

L-732, 138 treatment results in a large number of apoptotic cells were found in COLO 858, MEL HO and COLO 679 melanoma cell lines. In DAPI-stained cultures, at IC₅₀ concentration of 43.6% apoptotic cells for the three melanoma cell lines, whereas at IC₁₀₀ concentration of 51.4 % apoptotic cells^[1].
In Vivo: L-732138 (10^-4-10^-2 mol/kg; intravenous injection; for 15 minutes; male Dunkin-Hartley guinea-pigs) treatment abolishes vagally-induced plasma exudation and significantly inhibits the enhancement by LPS. The LPS-enhanced vagally-induced plasma exudation is not completely inhibited by either L-732138 or SOD pretreatment alone, but is blocked by the combination of both pretreatments^[3].