GABAAR/5-HT2AR modulator-1
GABAAR/5-HT2AR modulator-1 is an orally active and brain-penetrant GABAAR agonist and 5-HT2AR antagonist with Kd values of 0.89 and 0.78 μM. GABAAR/5-HT2AR modulator-1 blocks 5-HT-stimulated IP1 accumulation, inducing a chloride current, reduces LPS (HY-D1056)-induced increases of ROS, NO, TNF-α, IL-6, IL-1β, iNOS, and COX-2 levels. Antidepressant agent 11 dihydrochloride inhibits NF-κB pathway activation by reducing IκBα and p65 phosphorylation and blocking p65 nuclear translocation. GABAAR/5-HT2AR modulator-1 alleviates depression-like behaviors in LPS-challenged and chronic restraint stress-challenged mice, and protects hippocampal neurons against inflammation-mediated damage.
For research use only. We do not sell to patients.
- Formula: C18H31Cl2N3O3
- Molecular Weight:408.36
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
All 5-HT Receptor Isoforms
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Biological Activity
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5-HT2A Receptor 0.78 μM (Kd) |
GABAA 0.89 μM (Kd) |
IL-1β |
IL-6 |
COX-2 |
GABAAR/5-HT2AR modulator-1 (Compound 4f) binds to 5-HT2AR with a Kd of 0.78 μM and binds to GABAAR with a Kd of 0.89 μM[1].
GABAAR/5-HT2AR modulator-1 binds to 5-HT1AR, 5-HT6R, 5-HT7R, and D2R with Kd values of 5.94 μM, 3.62 μM, 2.96 μM, and 8.12 μM, respectively[1].
GABAAR/5-HT2AR modulator-1 inhibits hERG potassium channels with an IC50 >30 μM, indicating low cardiotoxic risk[1].
GABAAR/5-HT2AR modulator-1 has low cytotoxicity in HEK293T, BV2, and HT22 cells, with IC50 values >100 μM[1].
GABAAR/5-HT2AR modulator-1 acts as a 5-HT2AR antagonist in transfected HEK293T cells, blocking 5-HT-stimulated IP1 accumulation with an IC50 of 0.83 μM[1].
GABAAR/5-HT2AR modulator-1 (1 μM) functions as a GABAAR agonist in HEK293T cells stably expressing human α1β3γ2 GABAAR, inducing a chloride current amplitude of -726 pA[1].
GABAAR/5-HT2AR modulator-1 (5-20 μM) concentration-dependently reduces LPS (HY-D1056)-induced ROS and NO production in BV2 microglial cells[1].
GABAAR/5-HT2AR modulator-1 (5-20 μM) concentration-dependently reduces LPS-induced mRNA expression of TNF-α, IL-6, IL-1β, iNOS, and COX-2 in BV2 microglial cells[1].
GABAAR/5-HT2AR modulator-1 (5-20 μM) concentration-dependently reduces LPS-induced secretion of TNF-α, IL-6, and IL-1β in BV2 microglial cells[1].
GABAAR/5-HT2AR modulator-1 (5-20 μM) concentration-dependently reduces LPS-induced COX-2 and iNOS protein expression in BV2 microglial cells[1].
GABAAR/5-HT2AR modulator-1 (5-20 μM) concentration-dependently inhibits LPS-induced NF-κB pathway activation in BV2 microglial cells by reducing IκBα and p65 phosphorylation and blocking p65 nuclear translocation[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| Species | Dose | Route | Cmax | Tmax | AUC0-t | AUC0-∞ | T1/2 | Bioavailability | Tmax (Plasma) | Cmax (Brain) | Tmax (Brain) |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Mice[1] | 1 mg/kg | i.v. | 42.2 ng/mL | 0.083 h | 24.7 ng·h/mL | 25.4 ng·h/mL | 1.15 h | / | / | / | / |
| Mice[1] | 10 mg/kg | p.o. | 35.4 ng/mL | 0.417 h | 47.9 ng·h/mL | 50 ng·h/mL | 1.86 h | 19.4 % | / | / | / |
| Mice[1] | 10 mg/kg | p.o. | / | / | / | / | / | / | 0.5 h | 5.63 ng/mL | 2 h |
GABAAR/5-HT2AR modulator-1 (25-50 mg/kg; p.o.) dose-dependently alleviates stress-related depression-like behaviors in chronic restraint stress-exposed male ICR mice[1].
GABAAR/5-HT2AR modulator-1 (25-50 mg/kg; p.o.) exhibits significant antidepressant-like activity at oral doses of 25 mg/kg and 50 mg/kg in naive male ICR mice and shows no overt toxicological effects on major vital organs[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Depressent ICR mice (male, LPS-induced inflammation-driven depression)[1]
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Dosage:25 mg/kg; 50 mg/kg
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Administration:p.o.
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Result:Restored ambulatory activity and increased central zone entries in the open field test compared to LPS-treated mice.
Significantly reduced immobility time in the tail suspension test and forced swimming test, with the 50 mg/kg dose showing the most pronounced effect.
Dose-dependently reduced hippocampal mRNA levels of TNF-α, IL-6, IL-1β, iNOS, and COX-2.
Reduced serum levels of TNF-α, IL-6, and IL-1β.
Reduced hippocampal protein levels of iNOS and COX-2.
Dose-dependently restored hippocampal structural integrity via Nissl staining, with the 50 mg/kg dose exhibiting near-normal morphology.
Dose-dependently suppressed LPS-induced microglial activation via immunofluorescence staining, with the 50 mg/kg dose displaying near-complete normalization of microglial phenotype.
Chemical Information
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Molecular Weight 408.36
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Formula C18H31Cl2N3O3
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SMILES
COC1=CC=CC=C1N2CCN(CCCOC(CCCN)=O)CC2.Cl.Cl
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
GABAAR/5-HT2AR modulator-1 Related Classifications
HY-183357 Related Classifications
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