Synonym
A-381393; A 381393; A381393;
IUPAC/Chemical Name
2-[[4-(3,4-dimethylphenyl)piperazin-1-yl]methyl]-1H-benzimidazole
InChi Key
SAQMCVDGOIRQTC-UHFFFAOYSA-N
InChi Code
InChI=1S/C20H24N4/c1-15-7-8-17(13-16(15)2)24-11-9-23(10-12-24)14-20-21-18-5-3-4-6-19(18)22-20/h3-8,13H,9-12,14H2,1-2H3,(H,21,22)
SMILES Code
CC1=CC=C(N2CCN(CC3=NC4=CC=CC=C4N3)CC2)C=C1C
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
>2 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:
A-381393 is a brain penetrate dopamine D4 receptor antagonist, with Kis of 1.5, 1.9 and 1.6 nM for human dopamine D4.4, D4.2, and D4.7 receptor, respectively, >2700-fold selectivity over D1, D2, D3 and D5 dopamine receptors.
In vitro activity:
A-381393 binds to dopamine D4 receptor with nanomolar affinity (Ki = 1.5 nM), which is comparable with L-745870, and 36-fold higher than clozapine (Ki = 54 nM). A-381393 was more than 4000-fold selective for the dopamine D4 receptors as compared to dopamine D1, D2, D3 and D5 receptors.
Reference: Neuropharmacology. 2005 Jul;49(1):112-21. https://pubmed.ncbi.nlm.nih.gov/15992586/
In vivo activity:
It has been demonstrated that the dopamine D4 receptor selective agonist PD168077 induces penile erection in conscious rats by centrally mediated mechanisms with an effective dose of 0.3 μmol/kg. To determine if A-381393 would attenuate this effect, the compound was dosed subcutaneously at 30 μmol/kg before administration of PD168077. When the percent incidence of penile erection was examined, PD168077 induced 75% incidence at the efficacious dose. In animals treated with A-381393, this incidence was significantly reduced to 48% (Fig. 7).
Reference: Neuropharmacology. 2005 Jul;49(1):112-21. https://pubmed.ncbi.nlm.nih.gov/15992586/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
51.7 |
161.25 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
320.44
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. Nakane M, Cowart MD, Hsieh GC, Miller L, Uchic ME, Chang R, Terranova MA, Donnelly-Roberts DL, Namovic MT, Miller TR, Wetter JM, Marsh K, Stewart AO, Brioni JD, Moreland RB. 2-[4-(3,4-Dimethylphenyl)piperazin-1-ylmethyl]-1H benzoimidazole (A-381393), a selective dopamine D4 receptor antagonist. Neuropharmacology. 2005 Jul;49(1):112-21. doi: 10.1016/j.neuropharm.2005.02.004. Epub 2005 Apr 1. PMID: 15992586.
In vitro protocol:
1. Nakane M, Cowart MD, Hsieh GC, Miller L, Uchic ME, Chang R, Terranova MA, Donnelly-Roberts DL, Namovic MT, Miller TR, Wetter JM, Marsh K, Stewart AO, Brioni JD, Moreland RB. 2-[4-(3,4-Dimethylphenyl)piperazin-1-ylmethyl]-1H benzoimidazole (A-381393), a selective dopamine D4 receptor antagonist. Neuropharmacology. 2005 Jul;49(1):112-21. doi: 10.1016/j.neuropharm.2005.02.004. Epub 2005 Apr 1. PMID: 15992586.
In vivo protocol:
1. Nakane M, Cowart MD, Hsieh GC, Miller L, Uchic ME, Chang R, Terranova MA, Donnelly-Roberts DL, Namovic MT, Miller TR, Wetter JM, Marsh K, Stewart AO, Brioni JD, Moreland RB. 2-[4-(3,4-Dimethylphenyl)piperazin-1-ylmethyl]-1H benzoimidazole (A-381393), a selective dopamine D4 receptor antagonist. Neuropharmacology. 2005 Jul;49(1):112-21. doi: 10.1016/j.neuropharm.2005.02.004. Epub 2005 Apr 1. PMID: 15992586.
1: Marona-Lewicka D, Nichols DE. WAY 100635 produces discriminative stimulus effects in rats mediated by dopamine D(4) receptor activation. Behav Pharmacol. 2009 Feb;20(1):114-8. doi: 10.1097/FBP.0b013e3283242f1a. PubMed PMID: 19179855.
2: Marona-Lewicka D, Chemel BR, Nichols DE. Dopamine D4 receptor involvement in the discriminative stimulus effects in rats of LSD, but not the phenethylamine hallucinogen DOI. Psychopharmacology (Berl). 2009 Apr;203(2):265-77. doi: 10.1007/s00213-008-1238-0. PubMed PMID: 18604600.
3: Bitner RS, Nikkel AL, Otte S, Martino B, Barlow EH, Bhatia P, Stewart AO, Brioni JD, Decker MW, Moreland RB. Dopamine D4 receptor signaling in the rat paraventricular hypothalamic nucleus: Evidence of natural coupling involving immediate early gene induction and mitogen activated protein kinase phosphorylation. Neuropharmacology. 2006 Apr;50(5):521-31. PubMed PMID: 16324724.
4: Nakane M, Cowart MD, Hsieh GC, Miller L, Uchic ME, Chang R, Terranova MA, Donnelly-Roberts DL, Namovic MT, Miller TR, Wetter JM, Marsh K, Stewart AO, Brioni JD, Moreland RB. 2-[4-(3,4-Dimethylphenyl)piperazin-1-ylmethyl]-1H benzoimidazole (A-381393), a selective dopamine D4 receptor antagonist. Neuropharmacology. 2005 Jul;49(1):112-21. PubMed PMID: 15992586.
