L-745870 trihydrochloride, a potent, selective, brain-penetrant, and orally active dopamine D4 receptor antagonist, has a Ki of 0.43 nM. This compound demonstrates lower affinity for D2 (Ki of 960 nM) and D3 (Ki of 2300 nM) receptors, and moderate affinity for 5-HT2 receptors, sigma sites, and α-adrenoceptors[1][2][3].
体内研究
L-745870 exhibits strong pharmacokinetic properties, including 20-60% oral bioavailability and a plasma half-life of 2.1-2.8 hours in both rats and monkeys, along with excellent brain penetration, shown by high brain to plasma ratios in rats[1].
Following oral administration to squirrel monkeys, L745870 at 10 mg/kg induces mild sedation, and noticeable extrapyramidal motor symptoms, particularly bradykinesia, are evident at 30 mg/kg. Lower doses of L-745870 show no observable behavioral effects in monkeys[1].
体外研究
L-745870 effectively antagonizes D4 receptors' ability to inhibit agonist-induced stimulation of [35S]-GTPgS binding, blocks the suppression of forskolin-stimulated adenylate cyclase activity in HEK293 and CHO cells, prevents dopamine-induced suppression of Ca2+ currents in GH4C1 pituitary cells, inhibits D4 activation of G protein-coupled inwardly rectifying K+ channels, and counters dopamine-induced stimulation of extracellular acidification in transfected cells[1].
搜索
