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.
SB-222200 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Bone marrow-derived macrophages (BMDMs)
10 µM
1 hour
SB-222200 inhibits the activation of the NLRP3 inflammasome, reducing IL-1β release.
Cell Mol Life Sci. 2023 Jul 27;80(8):230
J774A.1 cells
10 µM
1 hour
SB-222200 effectively inhibits the activation of the NLRP3 inflammasome, reducing IL-1β release.
Cell Mol Life Sci. 2023 Jul 27;80(8):230
COS-7 cells
0.001–1000 µM
10 minutes
To study the antagonistic effect of SB-222200 on tiTac3Ra, results showed that SB-222200 had a strong inhibitory effect on tiTac3Ra with IC50 values of 84.11 μM (tiNKB) and 37.05 μM (tiNKF).
Biology (Basel). 2021 Sep 27;10(10):968
Rabbit iris sphincter muscle
0.3-3 µM
120 minutes
To evaluate the antagonistic effect of SB-222200 on [MePhe7]-NKB-induced contraction. Results showed that SB-222200 inhibited responses to low concentrations (<1 nM) of [MePhe7]-NKB to a greater extent than responses to higher concentrations (>1 nM) of [MePhe7]-NKB, and made the concentration-effect curves steeper and monophasic.
Br J Pharmacol. 1997 Oct;122(3):469-76
Rabbit iris sphincter muscle
30-300 nM
120 minutes
To evaluate the antagonistic effect of SB-222200 on senktide-induced contraction. Results showed that SB-222200 antagonized senktide-induced contraction in a surmountable and concentration-dependent manner, with a pA2 value of 7.89.
Br J Pharmacol. 1997 Oct;122(3):469-76
Human airway smooth muscle cells (HASM)
100 µM
30 minutes
SB-222200, as a selective NK3R antagonist, significantly inhibited senktide-induced inositol phosphate synthesis and intracellular Ca2+ concentration increase.
Am J Physiol Lung Cell Mol Physiol. 2008 Mar;294(3):L523-34
SB-222200 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
New Zealand White rabbits
Conscious rabbits
Intravenous injection
1 and 2 mg/kg
Single administration, observed for 30 minutes
To evaluate the inhibitory effect of SB-222200 on senktide-induced pupillary constriction. Results showed that SB-222200 significantly inhibited senktide-induced pupillary constriction, with a maximum inhibition of 100%.
Br J Pharmacol. 1997 Oct;122(3):469-76
C57BL/6 mice
MSU-induced peritonitis
Intraperitoneal injection
10, 15, 20 mg/kg
Single dose
SB-222200 dose-dependently reduced the production of IL-1β and IL-6 in the peritoneal fluid, alleviating MSU-induced peritonitis.
Cell Mol Life Sci. 2023 Jul 27;80(8):230
Nile tilapia (Oreochromis niloticus)
Adult male tilapia
Intraperitoneal injection
100 μg/kg
Single injection, observed for 2 hours
To study the effect of SB-222200 on LH and FSH release, results showed that SB-222200 significantly reduced LH plasma levels but had no significant effect on FSH levels.
Biology (Basel). 2021 Sep 27;10(10):968
CD-1 mice
Cocaine-induced hyperactivity model
Subcutaneous injection
2.5 or 5 mg/kg
Single dose or once daily for 5 days
To investigate the effects of SB 222200 on cocaine-induced hyperactivity. Results showed that acute administration of SB 222200 attenuated cocaine-induced stereotypic behavior, while repeated administration enhanced hyperactivity induced by cocaine or a low dose of SKF 82958.
Neuropharmacology. 2009 Sep;57(3):295-301
Caenorhabditis elegans
Wild-type and mutants
Culture medium administration
200 nM
Single dose, duration not specified
SB222200, a high-affinity human tachykinin receptor antagonist, increased the pharyngeal pumping rate in C. elegans
PLoS Biol. 2013 Nov;11(11):e1001712
Female C57Bl6/J mice
Ovariectomized (OVX) mice
Bilateral intra-MePD administration
4.20 pmol (initial dose) and 8.30 pmol (continuous dose)
Initial dose for 5 minutes, continuous dose for 65 minutes
To investigate whether SB222200 in the MePD can block the suppressive effect of predator odor (TMT) on LH pulsatility. Results showed that SB222200 completely blocked TMT-induced suppression of LH pulses.
J Neuroendocrinol. 2024 May;36(5):e13384
Mice
NK1 receptor knockout mice
Intravenous injection
5 mg/kg
Single dose, experiments conducted 15 minutes after administration
To evaluate the effect of SB-222200 on NKB-induced plasma extravasation in the lung, results showed that SB-222200 had no significant effect on NKB-induced plasma extravasation.
J Physiol. 2002 Sep 15;543(Pt 3):1007-14
Adult male CD-1 mice
Cocaine-induced behavioral sensitization model
Subcutaneous injection
5 mg/kg
Once daily for 5 days
Pretreatment with SB 222200 prevented the development of cocaine-induced behavioral sensitization and blocked the expression of sensitization when administered prior to a cocaine challenge. Additionally, SB 222200 reversed tolerance to increased GSK3 phosphorylation following repeated cocaine administration.
J Neurochem. 2010 Nov;115(3):635-42
Spontaneously hypertensive rats (SHR)
Spontaneously hypertensive rat model
Intracerebroventricular (i.c.v.) or ventral tegmental area (VTA) injection
500 pmol
Single injection, effect lasted for 8-10 hours
To investigate the antihypertensive effect of SB222200 in spontaneously hypertensive rats and its mechanism. Results showed that SB222200 produced antihypertensive effects via activation of dopamine D2 receptors in the ventral tegmental area.
Br J Pharmacol. 2010 Dec;161(8):1868-84
Mice
Pregnancy-induced hypertension and proteinuria model
Intravenous injection
75 μg/mL
Once on gestational day 13 and day 14
SB222200 treatment significantly reduced mean systolic pressure and proteinuria in CRP-infused pregnant mice, improved glomerular and placental damage, and decreased sFlt-1 levels
搜索
