Adenosine receptors are a family of GPCRs containing four subtypes (A1 , A2A , A2B and A3 receptors), all of which bind the ubiquitous nucleoside adenosine.[1]. Adenosine is a potent regulator of inflammation. Adenosine mediates its effects on inflammatory cells by engaging one or more cell-surface receptors[2]. SCH442416 is a potent, selective and brain-penetrant antagonist of adenosine A2A receptor (A2AR), with Kis of 0.048 and 0.5 nM for human and rat A2AR respectively[3]. SCH442416 displays more than 23000-fold selectivity over A1R, A2BR, and A3R (Ki=1111, 10000, and 10000 nM, respectively). It can be used for imaging of adenosine A2A receptors in rat and primate brain[4].
SCH-442416 (0.017 mg/kg; i.p.) completely abrogates the CGS-21680-induced decrease in skeletal muscle injury[5]. SCH442416 (1 μM) significantly attenuates the adenosine-induced dilation (from 15.3 to 5.6 μm)[6].
SCH442416 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Müller cells
100 nM
2 weeks
SCH442416 significantly increased Kir4.1 and TASK-1 protein expressions and enhanced inward potassium currents in Müller cells
Sci Rep. 2015 Jun 11;5:11294
Human subcutaneous fibroblasts (HSCF)
10 nM
28 days
SCH442416 blocked the A2A receptor, preventing the pro-fibrotic effects of AMP and CGS21680C on collagen production
Cells. 2020 Mar 7;9(3):651
HEK-293T cells
10 µM
5 minutes
To evaluate the inhibitory effect of MRS7145 on A2AR-mediated cAMP accumulation, results showed that MRS7145 significantly inhibited CGS21680-induced cAMP accumulation under light conditions
J Control Release. 2018 Aug 10;283:135-142
HEK-293T cells
1 µM
5 minutes
To evaluate the blocking effect of MRS7145 on A2AR ligand binding, results showed that MRS7145 effectively blocked APEC647 binding to A2AR under light conditions
J Control Release. 2018 Aug 10;283:135-142
MDA-MB-231 breast cancer cells
1 µM
72 hours
Evaluate the effect of A2AR antagonist on extracellular vesicle production, results showed SCH442416 significantly decreased exosome production.
Purinergic Signal. 2020 Jun;16(2):231-240
Mel526 metastatic melanoma cells
1 µM
72 hours
Evaluate the effect of A2AR antagonist on extracellular vesicle production, results showed SCH442416 significantly decreased exosome production.
Purinergic Signal. 2020 Jun;16(2):231-240
U251 glioblastoma cells
1 µM
72 hours
Evaluate the effect of A2AR antagonist on extracellular vesicle production, results showed SCH442416 significantly decreased exosome production.
Purinergic Signal. 2020 Jun;16(2):231-240
UMSCC47 cells
1 µM
72 hours
Evaluate the effect of A2AR antagonist on extracellular vesicle production, results showed SCH442416 stimulated exosome production under metabolic stress or cisplatin treatment.
Purinergic Signal. 2020 Jun;16(2):231-240
CHO cells
20 nM
at least 2 hours
To assess whether CBD interacts with the orthosteric site of the A2A receptor. Results showed that CBD was unable to significantly compete for the binding of the labeled antagonist to the receptor.
Int J Mol Sci. 2023 Dec 15;24(24):17500
Sheep brain striatum membranes
0.1 nM to 50 μM
To study the role of SCH442416 as an A2AR antagonist in competitive binding experiments, the results showed that SCH442416 could produce bell-shaped competition curves, indicating the existence of a ligand-competitor allosteric interaction.
Pharmacol Res. 2019 Jan;139:337-347
SCH442416 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Rat
Rat caudate putamen brain slices
Perfusion
1 µM
30 minutes
To test the role of A2A receptors in dopamine release modulation, results showed SCH442416 did not affect dopamine release
J Neurochem. 2015 Jan;132(1):51-60
Rats
6-hydroxydopamine (6-OHDA) hemi-parkinsonian rat model
Micro-pressure administration
1 µM
Single administration
SCH442416 significantly increased the spontaneous firing rate of pallidal neurons, indicating that endogenous adenosine modulates the activity of pallidal neurons through adenosine A 2A receptors
Front Physiol. 2017 Nov 7;8:897
Sprague Dawley rats
Chronic ocular hypertension (COH) model
Intravitreal injection
100 nM
Single injection, lasting 2 weeks
SCH442416 up-regulated Müller cell Kir4.1, TASK-1, GS and GLAST expressions and enhanced inward potassium currents, while increasing retinal ganglion cell (RGC) count
Sci Rep. 2015 Jun 11;5:11294
Mice
Unilateral 6-hydroxydopamine (6-OHDA)-lesioned Parkinson’s disease model
Intraperitoneal injection
3 mg/kg
Single administration, irradiation for 20 minutes
To evaluate the enhancing effect of MRS7145 on L-DOPA-induced contralateral rotations under light conditions, results showed that MRS7145 significantly potentiated the effect of L-DOPA under light conditions
J Control Release. 2018 Aug 10;283:135-142
Mice (C57BL/6)
Wild-type and CB1 receptor knockout mice
Intraperitoneal
3 mg/kg
Single injection, monitored for 30 min
SCH442416 robustly increased locomotor activity, an effect attenuated by CB1 receptor blockade or knockout
J Neurosci. 2010 Feb 10;30(6):2160-4
Rats
Bilateral common carotid artery occlusion (BCCAO) model
Intraperitoneal injection
3 mg/kg
Administered before BCCAO
To evaluate the effects of A2A receptors on rapid adenosine and oxygen dynamics during I/R. SCH 442416 eliminated the increase in adenosine and oxygen events caused by I/R.
ACS Chem Neurosci. 2019 Apr 17;10(4):1941-1949
Rats
Anesthetized rats
Intraperitoneal injection
3 mg/kg
Single dose, observed for 2 hours
SCH442416 significantly decreased the number of adenosine and oxygen transient events and increased the time interval between each transient release.
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