For research use only. Not for therapeutic Use.
A-381393 is a potent and selective agonist of the dopamine D4 receptor.
| Catalog Number | I000245 |
| CAS Number | 726174-00-1 |
| Synonyms | A-381393;2-[[4-(3,4-dimethylphenyl)piperazin-1-yl]methyl]-1H-benzimidazole |
| Molecular Formula | C20H24N4 |
| Purity | ≥95% |
| Target | dopamine D4 antagonist |
| Solubility | Soluble in DMSO |
| Storage | Store at RT |
| InChI | 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) |
| InChIKey | SAQMCVDGOIRQTC-UHFFFAOYSA-N |
| SMILES | CC1=CC=C(N2CCN(CC3=NC4=CC=CC=C4N3)CC2)C=C1C |
| Reference | 1:Neuropharmacology. 2005 Jul;49(1):112-21. Epub 2005 Apr 1. 2-[4-(3,4-Dimethylphenyl)piperazin-1-ylmethyl]-1H benzoimidazole (A-381393), a selective dopamine D4 receptor antagonist.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, PMID: 15992586 DOI: 10.1016/j.neuropharm.2005.02.004 </br><span>Abstract:</span> 2-[4-(3,4-Dimethylphenlyl)piperazin-1-ylmethyl]-1H benzoimidazole (A-381393) was identified as a potent dopamine D4 receptor antagonist with excellent receptor selectivity. [3H]-spiperone competition binding assays showed that A-381393 potently bound to membrane from cells expressing recombinant human dopamine D4.4 receptor (Ki=1.5 nM), which was 20-fold higher than that of clozapine (Ki=30.4 nM). A-381393 exhibited highly selective binding for the dopamine D4.4 receptor (>2700-fold) when compared to D1, D2, D3 and D5 dopamine receptors. Furthermore, in comparison to clozapine and L-745870, A-381393 exhibits better receptor selectivity, showing no affinity up to 10 microM for a panel of more than 70 receptors and channels, with the exception of moderate affinity for 5-HT2A (Ki=370 nM). A-381393 potently inhibited the functional activity of agonist-induced GTP-gamma-S binding assay and 1 microM dopamine induced-Ca2+ flux in human dopamine D4.4 receptor expressing cells, but not in human dopamine D2L or D3 receptor cells. In contrast to L-745870, A-381393 did not exhibit any significant intrinsic activity in a D4.4 receptor. In vivo, A-381393 has good brain penetration after subcutaneous administration. A-381393 inhibited penile erection induced by the selective D4 agonist PD168077 in conscious rats. Thus, A-381393 is a novel selective D4 antagonist that will enhance the ability to study dopamine D4 receptors both in vitro and in vivo. |
