Synonym
JNJ-10181457; RWJ 662733
IUPAC/Chemical Name
4-[[3-[4-(1-piperidinyl)-1-butyn-1-yl]phenyl]methyl]-morpholine, dihydrochloride
InChi Key
HDRIBIYPLKZUDQ-UHFFFAOYSA-N
InChi Code
InChI=1S/C20H28N2O/c1-3-10-21(11-4-1)12-5-2-7-19-8-6-9-20(17-19)18-22-13-15-23-16-14-22/h6,8-9,17H,1,3-5,10-16,18H2
SMILES Code
N1(CC2=CC=CC(C#CCCN3CCCCC3)=C2)CCOCC1
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>3 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
JNJ-10181457 is an antagonist of histamine H3 receptors.
In vivo activity:
Figure 7 shows that, in contrast to the rats pre-treated with saline (1 ml/kg, i.v.; left panel), i.v. pre-treatment with the selective H3 receptor antagonist, JNJ 10181457 (1 mg/kg; right panel), (i) completely blocked the inhibition of the vagally induced bradycardic responses produced by histamine (50 μg/kg) or methimepip (50 μg/kg), and (ii) had no effect per se on the vagally induced bradycardic responses induced in the animals receiving saline.
Reference: Basic Clin Pharmacol Toxicol. 2016 Feb;118(2):113-21. https://pubmed.ncbi.nlm.nih.gov/26301462/
Preparing Stock Solutions
The following data is based on the
product
molecular weight
385.37
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. García M, García-Pedraza JÁ, Villalón CM, Morán A. Pharmacological Evidence that Histamine H3 Receptors Mediate Histamine-Induced Inhibition of the Vagal Bradycardic Out-flow in Pithed Rats. Basic Clin Pharmacol Toxicol. 2016 Feb;118(2):113-21. doi: 10.1111/bcpt.12475. Epub 2015 Sep 14. PMID: 26301462.
2. Vanhanen J, Nuutinen S, Lintunen M, Mäki T, Rämö J, Karlstedt K, Panula P. Histamine is required for H₃ receptor-mediated alcohol reward inhibition, but not for alcohol consumption or stimulation. Br J Pharmacol. 2013 Sep;170(1):177-87. doi: 10.1111/bph.12170. PMID: 23489295; PMCID: PMC3764859.
In vivo protocol:
1. García M, García-Pedraza JÁ, Villalón CM, Morán A. Pharmacological Evidence that Histamine H3 Receptors Mediate Histamine-Induced Inhibition of the Vagal Bradycardic Out-flow in Pithed Rats. Basic Clin Pharmacol Toxicol. 2016 Feb;118(2):113-21. doi: 10.1111/bcpt.12475. Epub 2015 Sep 14. PMID: 26301462.
2. Vanhanen J, Nuutinen S, Lintunen M, Mäki T, Rämö J, Karlstedt K, Panula P. Histamine is required for H₃ receptor-mediated alcohol reward inhibition, but not for alcohol consumption or stimulation. Br J Pharmacol. 2013 Sep;170(1):177-87. doi: 10.1111/bph.12170. PMID: 23489295; PMCID: PMC3764859.
1. Bonaventure, P., Letavic, M., Dugovic, C., et al. Histamine H3 receptor antagonists: From target identification to drug leads. Biochem. Pharmacol. 73(8), 1084-1096 (2007).
2. Mohsen, A., Yoshikawa, T., Miura, Y., et al. Mechanism of the histamine H3 receptor-mediated increase in exploratory locomotor activity and anxiety-like behaviours in mice. Neuropharmacology 81, 188-194 (2014).
3. Iida, T., Yoshikawa, T., Kárpáti, A., et al. JNJ10181457, a histamine H3 receptor inverse agonist, regulates in vivo microglial functions and improves depression-like behaviours in mice. Biochem. Biophys. Res. Commun. 488(3), 534-540 (2017).
