For research use only. Not for therapeutic Use.
L-745870 hydrochloride is a potent, selective, brain-penetrant and orally active dopamine D4 receptor antagonist with a Ki of 0.43 nM. L-745870 hydrochloride shows weaker affinity for D2 (Ki of 960 nM) and D3 (Ki of 2300 nM) receptors, and exhibits moderate affinity for 5-HT2 receptors, sigma sites and α-adrenoceptors[1][2][3].
L-745870 is capable of antagonizing the ability of D4 receptors to inhibit agonist-induced stimulation of [35S]-GTPgS binding; blocking the inhibition of forskolin-stimulated adenylate cyclase activity in transfected human embryonic kidney (HEK293) and Chinese hamster ovary (CHO) cells; blocking dopamine-induced inhibition of Ca2+ currents in transfected GH4C1 pituitary cells; inhibiting D4 activation of cloned G protein-coupled inwardly rectifying K+ channels; and antagonizing dopamine-induced stimulation of extracellular acidification in transfected cells[1].
L-745870 has good pharmacokinetic properties (20-60% oral bioavailability and plasma t1/2 2.1-2.8 hours) in both rat and monkey, and excellent brain penetration with high brain to plasma ratios in rat[1].
Following oral administration to squirrel monkeys, L745870 (10 mg/kg p.o.) induces mild sedation and extrapyramidal motor symptoms, notably bradykinesia, became apparent at 30 mg/kg. Lower doses of L-745870 has no observable behavioural effects in monkeys[1].
| Catalog Number | I017523 |
| CAS Number | 1173023-36-3 |
| Synonyms | 3-[[4-(4-chlorophenyl)piperazin-1-yl]methyl]-1H-pyrrolo[2,3-b]pyridine;hydrochloride |
| Molecular Formula | C18H20Cl2N4 |
| Purity | ≥95% |
| InChI | InChI=1S/C18H19ClN4.ClH/c19-15-3-5-16(6-4-15)23-10-8-22(9-11-23)13-14-12-21-18-17(14)2-1-7-20-18;/h1-7,12H,8-11,13H2,(H,20,21);1H |
| InChIKey | GFFJYISJZJIKAF-UHFFFAOYSA-N |
| SMILES | C1CN(CCN1CC2=CNC3=C2C=CC=N3)C4=CC=C(C=C4)Cl.Cl |
| Reference | [1]. Bristow LJ, et al. Schizophrenia and L-745,870, a novel dopamine D4 receptor antagonist. Trends Pharmacol Sci. 1997 Jun;18(6):186-8. [2]. Patel S, et al. Biological profile of L-745,870, a selective antagonist with high affinity for the dopamine D4 receptor. J Pharmacol Exp Ther. 1997 Nov;283(2):636-47. [3]. 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. |
