Irdabisant hydrochloride
Irdabisant (CEP-26401) hydrochloride is a selective, orally active and blood-brain barrier (BBB) penetrant histamine H3 receptor (H3R) inverse agonist/inverse agonist with Ki values of 7.2 nM and 2.0 nM for rat H3R and human H3R, respectively. Irdabisant hydrochloride has relatively low inhibitory activity against hERG current with an IC50 of 13.8 μM. Irdabisant hydrochloride has cognition-enhancing and wake-promoting activities in the rat social recognition model. Irdabisant hydrochloride can be used to research schizophrenia or cognitive impairment.
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- CAS No.: 1005398-61-7
- Formule: C18H24ClN3O2
- Masse moléculaire:349.86
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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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Activité biologique
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rat H3 receptor 7.2 nM (Ki) |
human H3 receptor 2 nM (Ki) |
Irdabisant (CEP-26401, compound 8a) shows antagonist activity with Kb, app values of 1.0 nM and 0.4 nM for rat H3R and human H3R, respectively; shows inverse agonist activity with EC50 values of 2.0 nM and 1.1 nM for rat H3R and human H3R, respectively[1].
Irdabisant has moderate activity at Muscarinic M2 (Ki = 3.7 ± 0.0 μM) and Adrenergic α1A (Ki = 9.8 ± 0.3 μM) receptors, Dopamine transporters (Ki = 11 ± 2 μM), Norepinephrine transporters (Ki = 10 ± 1 μM), and phosphodiesterase PDE3 (IC50 = 15 ± 1 μM)[1].
Irdabisant inhibits the cytochrome P450 enzymes CYP1A2, 2C9, 2C19, 2D6, and 3A4 with IC50 values of greater than 30 μM, indicating less potential for drug-drug interactions[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
CEP-26401 (0.0001-0.1 mg/kg; i.v. or p.o.; single dosage) improves performance in the rat social recognition model of short-term memory[1].
CEP-26401 (3-30 mg/kg; p.o.; single dosage) exhibits wake-promoting activity in rat[2].
CEP-26401 (3-30 mg/kg; i.p.) increases prepulse inhibition (PPI) in DBA/2NCrl mice[2].
CEP-26401 (1 mg/kg for i.v. and 3 mg/kg for p.o.; single dosage) is rapidly absorbed with high oral bioavailability in rat and monkey, and shows a moderate clearance in monkey and dog compared to the rat[1].
Pharmacokinetic Parameters of Irdabisant (compound 8a) in rats, dogs and monkeys[1].
| Rat | Dog | Monkey | |
| i.v. t1/2 (h) | 2.6 | 2.9 | 5.4 |
| i.v. Vd (L/kg) | 9.4 | 3.5 ± 1.1 | 3.8 ± 0.9 |
| i.v. CL (mL/min/kg) | 42 | 13.2 ± 1.5 | 7.7 ± 1.8 |
| p.o. t1/2 (L/kg) | 2.9 | 2.7 | 5.0 |
| p.o. AUC (ng·h/mL) | 984 | 1190 ± 180 | 1919 ± 611 |
| p.o. Cmax (ng/mL) | 270 | 230 ± 70 | 760 ± 74 |
| p.o. F (%) | 83 | 22 ± 2 | 83 ± 18 |
| Brain to plasma ratio | 2.6 ± 0.2 | 2.4 ± 0.4 | / |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Male Sprague-Dawley rats (adult rats were briefly exposed to a juvenile rat for build social recognition model)[2]
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Dosage:0.0001, 0.001, 0.01 and 0.1 mg/kg for i.p.; 0.01 and 0.1 mg/kg for p.o.
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Administration:i.v. or p.o.; single dosage
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Result:Effectively reduced the ratio of investigation duration (RID) at doses over the range from 0.001 to 0.1 mg/kg i.p. and at 0.01 and 0.1 mg/kg p.o., demonstrating potent enhancement of short-term sensory memory in this model.
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Animal Model:Male Sprague-Dawley rats[2]
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Dosage:3, 10 and 30 mg/kg
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Administration:p.o.; single dosage
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Result:Exhibited robust wake promotion with the treated animals awake 90% of the time up to 3 h postdosing at 30 mg/kg.
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Animal Model:Male Sprague-Dawley rats, male beagle dogs and male cynomolgus monkeys[1]
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Dosage:1 mg/kg for i.v. and 3 mg/kg for p.o.
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Administration:i.v. and p.o.
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Result:Exhibited rapid absorption with high oral bioavailability in rat and monkey, and showed a moderate clearance in monkey and dog compared to the rat.
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Animal Model:Male DBA/2NCrl mice (19-27 g; 7-9 weeks)[2]
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Dosage:3, 10 and 30 mg/kg
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Administration:i.p.; single dosage
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Result:Increased prepulse inhibition (PPI) in DBA/2NCrl mice, whereas the antipsychotic Risperidone (HY-11018) is effective at 0.3 and 1 mg/kg i.p..
Chemical Information
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CAS No. 1005398-61-7
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Masse moléculaire 349.86
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Formule C18H24ClN3O2
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SMILES
C[C@H](CCC1)N1CCCOC2=CC=C(C(C=C3)=NNC3=O)C=C2.[H]Cl
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Synonyms
CEP-26401 hydrochloride
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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.
Pureté et documentation
Références
[1]. Hudkins RL, et al. Discovery and characterization of 6-{4-[3-(R)-2-methylpyrrolidin-1-yl)propoxy]phenyl}-2H-pyridazin-3-one (CEP-26401, irdabisant): a potent, selective histamine H3 receptor inverse agonist. J Med Chem. 2011 Jul 14;54(13):4781-92. [Content Brief]
[2]. Raddatz R, et al. CEP-26401 (irdabisant), a potent and selective histamine H₃ receptor antagonist/inverse agonist with cognition-enhancing and wake-promoting activities. J Pharmacol Exp Ther. 2012 Jan;340(1):124-33. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Irdabisant hydrochloride Related Classifications
HY-109968A Related Classifications
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