L-745870 hydrochloride 

L-745870 hydrochloride is a potent, selective, brain-penetrant and orally active dopamine D₄ receptor antagonist with a K_i of 0.43 nM. L-745870 hydrochloride shows weaker affinity for D₂ (K_i of 960 nM) and D₃ (K_i 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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

L-745870 has good pharmacokinetic properties (20-60% oral bioavailability and plasma t_1/2 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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

363.28

Solid

C₁₈H₂₀Cl₂N₄

1173023-36-3

[H]Cl.ClC(C=C1)=CC=C1N(CC2)CCN2CC3=CNC4=NC=CC=C43

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

• [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.  [Content Brief]

  [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.  [Content Brief]

  [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.  [Content Brief]