ADX88178 TFA
Based on 1 publication(s) in Google Scholar
ADX88178 TFA is an orally active, blood-brain barrier-penetrant, selective positive allosteric modulator of mGluR4, with an EC50 of 3.5 nM against hmGluR4. ADX88178 TFA modulates mGlu4 activity, enhances glutamate-mediated receptor activation, and increases the apparent affinity of glutamate for the receptor. ADX88178 TFA reverses haloperidol-induced catalepsy, potentiates the effects of levodopa (L-DOPA) and quinpirole, but fails to alleviate established abnormal involuntary movements, does not exacerbate L-DOPA-induced dyskinesia, and does not affect forelimb akinesia when administered alone. ADX88178 TFA can be used in research related to L-DOPA-induced dyskinesia and Parkinson's disease.
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- Formule: C14H13F3N6O2S
- Masse moléculaire:386.35
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
- Pureté et documentation
- Références
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Publications Citing Use of MedChemExpress (MCE) ADX88178 TFA
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Activité biologique
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hmGluR4 3.5 nM (EC50) |
ADX88178 (30 nM-3 μM) TFA potently enhances glutamate-mediated calcium mobilization in HEK293 cells expressing hmGluR4, with an EC50 of 3.5 nM, and exhibits no intrinsic agonist activity[2].
ADX88178 TFA enhances glutamate-mediated calcium mobilization in HEK293 cells expressing rat mGluR4, with an EC50 of 9.1 nM, and exhibits no intrinsic agonist activity[2].
ADX88178 TFA exerts inhibitory effects of varying intensities on cytochrome P450 enzymes, with the strongest inhibitory activity against CYP1A2 (IC50 = 0.46 μM) and weak inhibitory activity against CYP2D6 (IC50 >50 μM)[2].
ADX88178 (1000 ng/mL) TFA shows low plasma protein binding, with a free fraction of 8.1% in rat plasma and 21.5% in mouse plasma[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
ADX88178 (0.1-10 mg/kg; p.o.) produces dose-dependent reversal of haloperidol-induced catalepsy in male Sprague-Dawley rats, with an ED50 of 1.1 mg/kg and significant effects observed at 3 and 10 mg/kg[2].
ADX88178 (3-30 mg/kg; p.o.; 10 mg/kg; i.p.; 20-60 minutes before L-DOPA or vehicle) alone does not improve forelimb akinesia in 6-OHDA-lesioned male Sprague-Dawley rats, but it dose-dependently potentiates the efficacy of submaximal L-DOPA doses, with full reversal of motor deficits achieved at 30 mg/kg ADX88178 plus 6 mg/kg L-DOPA[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Sprague-Dawley (male, 270-300 g, 6-hydroxydopamine-lesioned, primed with L-DOPA + benserazide to establish stable AIMs)[1]
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Dosage:10 mg/kg; 30 mg/kg
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Administration:p.o.; single dose 30 min prior to L-DOPA + benserazide
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Result:Failed to produce a significant reduction in total AIMs scores compared to vehicle.
Failed to produce significant effects on axial, forelimb, or orolingual AIMs subtypes.
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Animal Model:Sprague-Dawley (male, 260-450 g, haloperidol-induced catalepsy)[2]
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Dosage:0.1 mg/kg; 0.3 mg/kg; 1 mg/kg; 3 mg/kg; 10 mg/kg
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Administration:p.o.
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Result:Produced a dose-dependent reversal of catalepsy.
Reduced catalepsy latency to 33.4 seconds (a 62.3% reduction from haloperidol alone) at 3 mg/kg.
Reduced catalepsy latency to 25.7 seconds (a 71.0% reduction from haloperidol alone) at 10 mg/kg.
Achieved an ED50 of 1.1 mg/kg for catalepsy reversal.
Reached an in vivo plasma EC50 of 92 ng/mL (338 nM).
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Animal Model:Sprague-Dawley (male, 225-300 g, bilateral striatal 6-hydroxydopamine lesions)[2]
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Dosage:3-30 mg/kg (p.o.); 10 mg/kg (i.p.)
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Administration:p.o.; i.p.;
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Result:Showed no significant effect on forelimb stepping scores when administered alone at 3, 10, or 30 mg/kg p.o.
Increased forelimb steps to ~18 when coadministered with 6 mg/kg L-DOPA at 3 mg/kg p.o.
Increased forelimb steps to ~23 when coadministered with 6 mg/kg L-DOPA at 10 mg/kg p.o.
Fully reversed forelimb stepping deficit, restoring steps to pre-lesion levels (~35) when coadministered with 6 mg/kg L-DOPA at 30 mg/kg p.o.
Potentiated L-DOPA efficacy at 10 mg/kg i.p., allowing full reversal of akinesia at 60 mg/kg L-DOPA (vs. 120 mg/kg L-DOPA alone).
Chemical Information
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Masse moléculaire 386.35
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Formule C14H13F3N6O2S
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SMILES
CC1=C(C2=CNN=C2)N=C(NC3=NC=CC(C)=N3)S1.OC(C(F)(F)F)=O
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Publications (1)
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Journal Impact Factor
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Most Recent
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Cell Res
Structural insights into dimerization and activation of the mGlu2-mGlu3 and mGlu2-mGlu4 heterodimers. [Abstract]2023 Oct;33(10):762-774. PMID: 37286794
Pureté et documentation
Références
[1]. Finlay CJ, et al. Metabotropic Glutamate Receptor 4 (mGlu4) Positive Allosteric Modulators Lack Efficacy in Rat and Marmoset Models of L-DOPA-Induced Dyskinesia. J Parkinsons Dis. 2024;14(2):245-259. [Content Brief]
[2]. Le Poul E, et al. A potent and selective metabotropic glutamate receptor 4 positive allosteric modulator improves movement in rodent models of Parkinson's disease. J Pharmacol Exp Ther. 2012;343(1):167-177. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
ADX88178 TFA Related Classifications
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