AZD3783
AZD3783 is an orally active, blood-brain barrier-penetrant 5-HT1B receptor antagonist. AZD3783 reverses agonist-induced hypothermia, inhibits separation-induced vocalizations in guinea pig pups, and acts as a moderately permeable glycoprotein substrate with moderate clearance. AZD3783 inhibits hERG channel activity. AZD3783 is applicable for research on depression, anxiety disorders, and other psychiatric diseases associated with serotonergic neurotransmission.
For research use only. We do not sell to patients.
- CAS No.: 1162658-64-1
- Formula: C26H34N4O4
- Molecular Weight:466.57
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Protocols
- Purity & Documentation
- References
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Help & FAQs
All 5-HT Receptor Isoforms
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Biological Activity
Description
IC50 & Target
[1]|
5-HT1B Receptor 12.5 nM (Ki) |
In Vitro
AZD3783 (Compound 1a) binds to human 5-HT1B receptors expressed on CHO cell membranes, with a Ki value of 12 nM[1].
AZD3783 (1 h) acts as a functional antagonist of the 5-HT1B receptor expressed on human CHO cell membranes, and produces 120% inhibition of 5-HT-stimulated GTPγS binding[1].
AZD3783 inhibits hERG channel activity in cell-based in vitro assays, with an IC50 of 19 μM and a maximal effect of 81% at a concentration of 100 μM[1].
AZD3783 (300 μM) exhibits pro-phospholipidogenic activity in in vitro cell assays, producing 81% of the maximum effect at a concentration of 300 μM[1].
AZD3783 (170 pM-10 μM; 1 h) exhibits high affinity for recombinant human 5-HT1B receptor, with a Ki value of 12.5 nM[2].
AZD3783 (170 pM-10 μM; 1 h) exhibits high affinity for recombinant guinea pig 5-HT1B receptors, with a Ki value of 11.1 nM[2].
AZD3783 (170 pM-10 μM; 1 h) is a reversible competitive antagonist of the recombinant human 5-HT1B receptor, with an EC50 of 42 nM for inhibiting 5-HT-induced GTPγ[35S] binding[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
Parmacokinetics
| Species | Dose | Route | AUC0-∞ | CLplasma | Vdss | T1/2 | Cmax | Tmax | Bioavailability |
|---|---|---|---|---|---|---|---|---|---|
| Rat[2] | 10 μmol/Kg | i.v. | 8.8 μM·h | 19 mL/min/kg | 2.3 L/kg | 1.4 h | / | / | / |
| Rat[2] | 30 μmol/Kg | p.o. | 26 μM·h | / | / | / | 9.5 μM | 0.25 h | 98 % |
| Dog[2] | 2.0 μmol/Kg | i.v. | 1.9 μM·h | 18 mL/min/kg | 4.3 L/kg | 3.7 h | / | / | / |
| Dog[2] | 2.0 μmol/Kg | p.o. | 1.1 μM·h | / | / | / | 0.24 μM | 1.00 h | 58 % |
| Monkey[2] | 3.0 μmol/Kg | i.v. | 1.5 μM·h | 35 mL/min/kg | 5.9 L/kg | 4.6 h | / | / | / |
In Vivo
AZD3783 (0.2-2.0 μmol/kg; subcutaneous injection; single administration) reduces separation-induced vocalizations in guinea pig pups at doses as low as 0.2 μmol/kg, exhibiting anxiolytic-like activity[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Dunkin-Hartley (adult, male, body weight 0.2 to 0.4 kg)[2]
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Dosage:0.002, 0.006, 0.06, 0.2, 0.6, 2, 6, 20 μM/kg
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Administration:s.c.; single dose
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Result:Reversed CP135.807-induced hypothermia in a dose-dependent manner.
Achieved an unbound plasma EC50 of 18 nM for blockade of hypothermia.
Achieved an unbound brain EC50 of 16 nM for blockade of hypothermia.
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Animal Model:Dunkin-Hartley (pups, 4 to 6 days postnatal to 23 to 25 days postnatal)[2]
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Dosage:0.2, 0.6, 2.0 μM/kg
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Administration:s.c.; single dose per test session
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Result:Significantly decreased separation-induced vocalizations overall.
Produced significant reductions in vocalizations at all tested doses.
Demonstrated a minimum efficacious dose at or below 0.2 μM/kg.
Chemical Information
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CAS No. 1162658-64-1
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Molecular Weight 466.57
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Formula C26H34N4O4
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SMILES
O=C([C@@H]1OC2=C(N3CCN(CC3)C)C=C(C=C2CC1)OC)NC4=CC=C(N5CCOCC5)C=C4
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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.
Protocols
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Protocol for Pharmacokinetic Study
Pharmacokinetic studies quantify how an organism handles a drug over time through absorption, distribution, metabolism, and excretion, and the core experimental readout is the concentration-time profile of parent drug and, when relevant, metabolites in biological matrices such as plasma, whole blood, urine, bile, or tissue. Pharmacokinetic analysis links dose, route, exposure, clearance, half-life, distribution, bioavailability, and systemic exposure to drug efficacy and toxicity hypotheses rather than measuring a signaling pathway directly. The literature links pharmacokinetics to drug-development phenotypes by showing that drug metabolism and pharmacokinetics influence compound progression, exposure-response interpretation, safety margins, dosing strategy, and failure risk during discovery and development. DMPK science contributes to compound optimization by integrating physicochemical properties, in vitro metabolism, transporter behavior, in vivo exposure, and pharmacodynamic contex
Purity & Documentation
References
[1]. Nugiel DA, et al. De novo design of a picomolar nonbasic 5-HT(1B) receptor antagonist. J Med Chem. 2010 Feb 25;53(4):1876-80. [Content Brief]
[2]. Zhang M, et al. Preclinical pharmacology and pharmacokinetics of AZD3783, a selective 5-hydroxytryptamine 1B receptor antagonist. J Pharmacol Exp Ther. 2011;339(2):567-578. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
AZD3783 Related Classifications
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