同义名 :	-
	CAS号 :	174635-69-9
	货号 :	A875802
	分子式 :	C26H24N2O
	纯度 :	99%+
	分子量 :	380.48
	MDL号 :	MFCD00944072
	存储条件：	Pure form Sealed in dry, 2-8°C In solvent -20°C:3-6个月-80°C:12个月
	溶解度 :	-
	动物实验配方：

生物活性

描述

NK-3 receptors are G-protein coupled receptors activated by mammalian tachykinins, which can modulate dopaminergic neurotransmission, and thus may play a role in development and expression of behavioral sensitization[3]. SB-222200 is a human NK-3 receptor (hNK-3R) antagonist. SB-222200 inhibited 125I-[MePhe7] neurokinin B (NKB) binding to Chinese hamster ovary (CHO) cell membranes stably expressing the hNK-3 receptor with a Ki of 4.4 nM and antagonized NKB-induced Ca2+ mobilization in HEK 293 cells stably expressing the hNK-3 receptor with an IC50 of 18.4 nM. SB-222200 was selective for hNK-3 receptors compared with hNK-1 (Ki > 100,000 nM) and hNK-2 receptors (Ki = 250 nM). In HEK 293 cells transiently expressing murine NK-3 receptors, SB-222200 inhibited binding of 125I-[MePhe7]NKB (Ki = 174 nM) and antagonized NKB (1 nM)-induced calcium mobilization (IC50 = 265 nM). In mice oral administration of SB-222200 produced dose-dependent inhibition of behavioral responses induced by i.p. or intracerebral ventricular administration of the NK-3 receptor-selective agonist, senktide, with ED50 value of approximately 5 mg/kg. Pharmacokinetic evaluation of SB-222200 in rat after oral administration (8 mg/kg) indicated sustained plasma concentrations (Cmax) = 400 ng/mL) and bioavailability of 46% [2]. Administration of SB-222200 (5 mg/kg, s.c.) prior to repeated cocaine (20 mg/kg, i.p.) prevented the development of sensitized responses after a cocaine challenge.

实验方案
	1mg	5mg	10mg
1 mM 5 mM 10 mM	2.63mL 0.53mL 0.26mL	13.14mL 2.63mL 1.31mL	26.28mL 5.26mL 2.63mL

参考文献

[1]King AG, Sanger GJ. Effect of a selective and potent central nervous system penetrant, neurokinin-3 receptor antagonist (SB-222200), on cisplatin-induced emesis in the ferret. Neurosci Lett. 2005 Mar 7;376(1):5-8. [2]Sarau HM, Griswold DE, Bush B, et al. Nonpeptide tachykinin receptor antagonists. II. Pharmacological and pharmacokinetic profile of SB-222200, a central nervous system penetrant, potent and selective NK-3 receptor antagonist. J Pharmacol Exp Ther. 2000;295(1):373-381. [3]Nwaneshiudu CA, Unterwald EM. NK-3 receptor antagonism prevents behavioral sensitization to cocaine: a role of glycogen synthase kinase-3 in the nucleus accumbens. J Neurochem. 2010;115(3):635-642.