| Description | L-741626 (3-(4-(4-Chlorophenyl-4-hydroxypiperidino)methyl)indole) is a selective antagonist of D2 dopamine receptor (Ki: 2.4, 100, and 220 nM for human D2, D3 and D4 receptors respectively). |
| In vitro | L-741626 is an effective antagonist (EC50 (D2)=4.46 nM) with some D2 selectivity (EC50 (D3)=90.4 nM), in the functional assay. L-741626 is prepared by literature methods (Ki (D2)=11.2 nM). L-741626 also shows a D3/D2 and D4/D2 selectivity ratio of 15-fold and 136-fold, respectively. Intrinsic activities using inhibition of quinpirole stimulation of mitogenesis in human dopamine D2 or D3 receptors transfected into Chinese hamster ovary (CHO) cells, in a functional assay [2]. |
| In vivo | In pramipexole-trained male Sprague Dawley rats, L-741626 (1.0 mg/kg; i.h.) is effective at shifting to the right the pramipexole dose-response curve [3]. Coadministration Cocaine with the D2 antagonist L-741626 (3 mg/kg; i.p.; 15 min before Cocaine) for 5 days decreases the Cocaine-induced enhance in microglial TNF-α production in adult mice [4]. |
| Target activity | D2 receptor (human):(ki)2.4 nM, D3 receptor (human):100 nM(ki), D4 receptor (human):220 nM(ki) |
| Synonyms | 3-(4-(4-Chlorophenyl-4-hydroxypiperidino)methyl)indole |
| molecular weight | 340.85 |
| Molecular formula | C20H21ClN2O |
| CAS | 81226-60-0 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 40 mg/mL (117.35 mM), Sonication is recommended. |
| References | 1. Lewitus GM, et al. Microglial TNF-α Suppresses Cocaine-Induced Plasticity and Behavioral Sensitization. Neuron. 2016 May 4;90(3):483-91. 2. Grundt P, et al. Analogues of the dopamine D2 receptor antagonist L741,626: Binding, function, and SAR. Bioorg Med Chem Lett. 2007 Feb 1;17(3):745-9. 3. Koffarnus MN, et al. The discriminative stimulus effects of dopamine D2- and D3-preferring agonists in rats. Psychopharmacology (Berl). 2009 Apr;203(2):317-27. 4. Kulagowski JJ, et al. 3-((4-(4-Chlorophenyl)piperazin-1-yl)-methyl)-1H-pyrrolo-2,3-b-pyridine: an antagonist with high affinity and selectivity for the human dopamine D4 receptor. J Med Chem. 1996 May 10;39(10):1941-2. |