L-745870 is a high-affinity and selective human dopamine D4 receptor antagonist (Ki: 0.43 nM). L-745870 has excellent brain penetration. It considerably weaker D2 (Ki: 960 nM) and D3 (Ki: 2300 nM) receptors affinity.

D2 receptor (human):960 nM(ki), D4 receptor (human):(ki)0.43 nM, D3 receptor (human):2300 nM(ki)

L-745870 is an antagonist at human D4 receptors which displayed in vitro pharmacological studies. In that L-745870 is capable of antagonizing the ability of D4 receptors to inhibit agonist-induced stimulation of [35S]-GTPgS binding. It blocking the inhibition of forskolin-stimulated adenylate cyclase activity in the transfected human embryonic kidney (HEK293) and Chinese hamster ovary (CHO) cells and also blocking dopamine-induced inhibition of Ca2+ currents in transfected GH4C1 pituitary cells. L-745870 inhibiting D4 activation of cloned G protein-coupled inwardly rectifying K+ channels and antagonizing dopamine-induced stimulation of extracellular acidification in transfected cells[1][2].

L-745870 demonstrates favorable pharmacokinetic properties (20-60% oral bioavailability, plasma t1/2 2.1-2.8 hours) in both rats and monkeys, and exhibits excellent brain penetration with high brain-to-plasma ratios in rats. While L-745870 does not affect apomorphine-induced stereotypy in rats, it induces catalepsy in mice at a high dose of 100 mg/kg p.o. likely due to D2 receptor occupancy. Surrogate marker assays indicate that L-745870 is biologically active in the brain, with doses ranging from 5 to 60 mg/kg p.o. occupying 50% of brain D4 receptors. In squirrel monkeys, oral administration of L-745870 (10 mg/kg) causes mild sedation and extrapyramidal motor symptoms, with bradykinesia apparent at 30 mg/kg. High doses may induce extrapyramidal symptoms in primates by sufficient antagonism of D2 receptors in the CNS. Lower doses show no observable behavioral effects in monkeys [1][2].