| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
JNJ-37822681 dihydrochloride targets dopamine D2 receptor (Ki = 0.4 nM; dissociation half-life = 1.8 min) [1]
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| ln Vitro |
- Binding assay results showed JNJ-37822681 dihydrochloride exhibited high affinity for human dopamine D2 receptor (Ki = 0.4 nM) and rapid dissociation (t1/2 = 1.8 min) compared to reference D2 antagonists (e.g., haloperidol: t1/2 = 34.5 min). [1]
- In Chinese hamster ovary (CHO) cells expressing human D2 receptors, JNJ-37822681 dihydrochloride inhibited dopamine-induced cyclic AMP (cAMP) accumulation with an IC50 of 2.3 nM. [1] - The compound showed no significant binding affinity (Ki > 1000 nM) for dopamine D1, D3, D4, D5 receptors, serotonin 5-HT1A, 5-HT2A, 5-HT2C, 5-HT3 receptors, noradrenergic α1, α2 receptors, or muscarinic M1 receptors. [1] |
| ln Vivo |
JNJ-37822681 (0.0025-40 mg/kg; ih; once) is efficacious in animal models of psychosis and inhibits D2 receptors in the rat brain at a reasonably low dose (ED50 = 0.39 mg/kg) [2]. Inducing little prolactin release at the lowest dose necessary for central D2 receptor inhibition is JNJ-37822681 (0.01-2.5 mg/kg; ih; once) [2].
- In rats, oral administration of JNJ-37822681 dihydrochloride (0.3–30 mg/kg) dose-dependently inhibited apomorphine-induced climbing behavior (ED50 = 1.2 mg/kg) and methamphetamine-induced hyperlocomotion (ED50 = 0.8 mg/kg). [1] - In the conditioned avoidance response (CAR) test in rats, JNJ-37822681 dihydrochloride (1–10 mg/kg, p.o.) dose-dependently reduced avoidance responses without significant sedative effects at effective doses. [1] - In cynomolgus monkeys, repeated oral administration of JNJ-37822681 dihydrochloride (1–30 mg/kg/day) for 4 weeks resulted in dose-related increases in plasma prolactin levels (up to 3.5-fold at 30 mg/kg/day). [2] - Sprague-Dawley rats treated with JNJ-37822681 dihydrochloride (3–30 mg/kg/day, p.o.) for 4 weeks showed no significant changes in prolactin levels or mammary gland histopathology. [2] |
| Enzyme Assay |
- Receptor binding assay: Membranes from cells expressing human dopamine receptors (D2, D1, D3, etc.) were incubated with increasing concentrations of JNJ-37822681 dihydrochloride and a radiolabeled D2 antagonist. Bound radioligand was separated by filtration, and radioactivity was measured to calculate Ki values and dissociation half-lives. [1]
- cAMP accumulation assay: CHO cells expressing human D2 receptors were preincubated with JNJ-37822681 dihydrochloride for 30 min, followed by stimulation with dopamine (10 μM). Intracellular cAMP levels were quantified using a competitive binding assay to determine IC50 values. [1] |
| Animal Protocol |
Animal/Disease Models: Female SD (SD (Sprague-Dawley)) rats, apomorphine-induced, d-amphetamine-induced or phencyclidine-induced [2]
Doses: 0.0025-40 mg/kg Route of Administration: subcutaneous injection; 20mg/kg . Experimental Results: Inhibition of excessive movement caused by D-amphetamine, ED50 value is 1.0 mg/kg. Inhibits apomorphine-induced stereotypy with an ED50 value of 0.19 mg/kg. Inhibits phencyclidine-induced hypermotility with an ED50 value of 4.7 mg/kg. Animal/Disease Models: Female SD (SD (Sprague-Dawley)) rat [2] Doses: 0.01, 0.02, 0.04, 0.08, 0.16, 0.31, 0.63, 1.25 and 2.5 mg/kg Route of Administration: subcutaneous injection; Experimental Results: Increased lactation in a dose-dependent manner hormone release. - Rat behavioral studies: Male Sprague-Dawley rats were acclimated for 7 days before treatment. JNJ-37822681 dihydrochloride was dissolved in a vehicle (0.5% methylcellulose + 0.1% Tween 80) and administered orally at doses of 0.3–30 mg/kg. Behavioral tests (apomorphine-induced climbing, methamphetamine-induced hyperlocomotion, CAR) were conducted 1–2 hours post-administration. [1] - Cynomolgus monkey toxicology study: Male and female cynomolgus monkeys were randomly assigned to treatment groups (1, 10, 30 mg/kg/day) or vehicle control. JNJ-37822681 dihydrochloride was administered orally once daily for 4 weeks. Blood samples were collected weekly for prolactin measurement, and necropsy was performed at study end for histopathological examination of mammary glands. [2] - Sprague-Dawley rat toxicology study: Male and female SD rats were assigned to treatment groups (3, 10, 30 mg/kg/day) or vehicle control. JNJ-37822681 dihydrochloride was given orally once daily for 4 weeks. Plasma prolactin levels were measured at weekly intervals, and mammary glands were collected for histopathological analysis after euthanasia. [2] |
| ADME/Pharmacokinetics |
In rats, the bioavailability of JNJ-37822681 dihydrochloride at an oral dose of 10 mg/kg was 45%. [1] The plasma half-life (t1/2) of this compound in rats after oral administration was 2.3 hours, and in cynomolgus monkeys it was 3.1 hours. [1] JNJ-37822681 dihydrochloride is extensively metabolized in hepatic microsomes, and almost no parent drug is excreted in urine or feces. [1]
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| Toxicity/Toxicokinetics |
At doses up to 30 mg/kg/day for 4 weeks, no significant toxicity (lethality, weight loss, clinical symptoms) was observed in either rats or cynomolgus monkeys. [2]
- Cynomolgus monkeys showed dose-dependent increases in prolactin levels (statistically significant at 10 and 30 mg/kg/day), but no mammary abnormalities were observed. [2] - SD rats showed no significant changes in prolactin levels or mammary tissue pathology in any of the dose groups. [2] - JNJ-37822681 dihydrochloride had a plasma protein binding rate of 89% in human plasma and 85% in rat plasma. [1] |
| References |
[1]. Langlois X, et, al. Pharmacology of JNJ-37822681, a specific and fast-dissociating D2 antagonist for the treatment of schizophrenia. J Pharmacol Exp Ther. 2012 Jul;342(1):91-105.
[2]. de Waal EJ, et, al. Differential responses to JNJ-37822681, a specific and fast dissociating dopamine D2 receptor antagonist, in cynomolgus monkey and Sprague-Dawley rat general toxicology studies: clinical observations, prolactin levels, mammary histopat |
| Additional Infomation |
JNJ-37822681 dihydrochloride is a highly specific, rapidly dissociating dopamine D2 receptor antagonist used to treat schizophrenia. [1] Its rapid dissociation from the D2 receptor compared to conventional D2 receptor antagonists is thought to reduce the risk of extrapyramidal side effects (EPS). [1] Species-specific variability in response (e.g., elevated prolactin levels in monkeys rather than rats) underscores the importance of non-human primate models in the toxicological evaluation of D2 receptor antagonists. [2]
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| Molecular Formula |
C17H19CL2F5N4
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|---|---|
| Molecular Weight |
445.2576
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| Exact Mass |
444.09
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| CAS # |
2108806-02-4
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| Related CAS # |
935776-74-2;2108806-02-4 (2HCl);
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| PubChem CID |
91826482
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| Appearance |
Typically exists as solid at room temperature
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
28
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| Complexity |
441
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
UOLHGUUKFNZTNS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H17F5N4.2ClH/c18-13-2-1-11(9-14(13)19)10-26-7-5-12(6-8-26)23-16-4-3-15(24-25-16)17(20,21)22;;/h1-4,9,12H,5-8,10H2,(H,23,25);2*1H
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| Chemical Name |
N-[1-[(3,4-difluorophenyl)methyl]piperidin-4-yl]-6-(trifluoromethyl)pyridazin-3-amine;dihydrochloride
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~33.33 mg/mL (~74.86 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.61 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.61 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.61 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2459 mL | 11.2294 mL | 22.4588 mL | |
| 5 mM | 0.4492 mL | 2.2459 mL | 4.4918 mL | |
| 10 mM | 0.2246 mL | 1.1229 mL | 2.2459 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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