| Description: |
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]. |
| Target: |
NK1:2.3 nM (IC50) |
| 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]. Animal Model: Male Dunkin-Hartley guinea-pigs (350-500 g) injected with lipopolysaccharide (LPS)[3] Dosage: 10-4 mol/kg , 10-3 mol/kg and 10-2 mol/kg Administration: Intravenous injection; for 15 minutes Result: Abolished the vagally-induced plasma leakage in tracheobronchial tissues, and dose-dependently inhibited the LPS enhanced vagally-induced plasma exudation in traceobronchial tissues. |
| In Vitro: |
L-732138 (0 -100 µM; 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 μM for COLO 858 cells, 76.3 μM for MEL HO cells and 64.2 μM 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]. Cell Proliferation Assay[1] Cell Line: COLO 858, MEL HO and COLO 679 cells Concentration: 0 µM, 20 µM, 40 µM, 60 µM, 80 µM, 100 µM Incubation Time: First doubling time Result: Resulted in a concentration-dependent cytotoxicity. |
| References: |
[1]. Muñoz M, et al. The NK-1 Receptor Antagonist L-732,138 Induces Apoptosis and Counteracts Substance P-Related Mitogenesis in Human Melanoma Cell Lines. Cancers (Basel). 2010 Apr 20;2(2):611-23.
[2]. Cascieri MA, et al. Characterization of the interaction of N-acyl-L-tryptophan benzyl ester neurokinin antagonists with the human neurokinin-1 receptor. J Biol Chem. 1994 Mar 4;269(9):6587-91.
[3]. Kuo HP, et al. Lipopolysaccharide enhances neurogenic plasma exudation in guinea-pig airways. Br J Pharmacol. 1998 Oct;125(4):711-6. |
