L-745870 trihydrochloride is a potent, selective, brain-penetrant and orally activedopamineD₄receptorantagonist with aK_iof 0.43 nM. L-745870 trihydrochloride shows weaker affinity for D₂(K_iof 960 nM) and D₃(K_iof 2300 nM) receptors, and exhibits moderate affinity for 5-HT₂receptors, 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 t_1/22.1-2.8 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].

436.21

C₁₈H₂₂Cl₄N₄

866021-03-6

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.