L-733,060 hydrochloride

L-733060 hydrochloride is a potent tachykinin NK1 receptor antagonist. L-733060 hydrochloride inhibits neurogenic plasma extravasation at doses that do not cause adverse cardiovascular effects in rodents and also acts as an antitumoral agent[1][2].

Research Areas >> Cancer

Signaling Pathways >> Neuronal Signaling >> Neurokinin Receptor

Research Areas >> Neurological Disease

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

NK1

L-733060 (30-300 nM) inhibits the [Ca2+]i mobilisation caused by substance P (100 nM) in a concentration-dependent manner in human tachykinin NK1 receptor-transfected CHO cells[1]. L-733060 (2.5-20 μM; 48 and or 96 h) results in a concentration-dependent cytotoxicity in COLO 858 cells[2]. L-733060 (10-30 μM; 24 and 48 h) inhibits MEL H0 cells proliferation with IC50s of 27.5 μM and 18.9 μM at 24 h and 48 h, respectively[2]. L-733060 (20-50 μM; and or 72 h) inhibits COLO 679 cells growth with IC50s of 33.8 μM and 31.5 μM at 30 h and 72 h, respectively[2]. Cell Proliferation Assay[2] Cell Line: COLO 858 cells Concentration: 2.5, 5, 10, 20 μM Incubation Time: 0, 48, 96 h Result: Inhibited cells growth with IC50s of 8.7 μM and 7.1 μM at 48 h and 96 h, respectively.

L-733060 (10-1000 μg/kg; i.v.) inhibits electrically stimulated plasma extravasation in dura mater of rats[1]. L-733060 (300-3000 μg/kg; i.v.) has no significant hypotensive or bradycardic effects are observed at doses of <3000 μg/kg in conscious or anaesthetised rats[1]. Animal Model: Male Sprague-Dawley rats (200 g) with electrical stimulation of the trigeminal ganglion[1] Dosage: 10, 100, 1000 mg/kg Administration: I.v. injection Result: Produced a significant dose-related inhibition of plasma extravasation with an ID50 of 212±19 μg/kg.

[1]. Seabrook GR, et, al. L-733,060, a novel tachykinin NK1 receptor antagonist; effects in [Ca2+]i mobilisation, cardiovascular and dural extravasation assays. Eur J Pharmacol. 1996 Dec 12; 317(1):129-35.

[2]. Muñoz M, et, al. Antitumoral action of the neurokinin-1 receptor antagonist L-733 060 on human melanoma cell lines. Melanoma Res. 2004 Jun;14(3):183-8.