L-745870 hydrochloride is a robust, selective, brain-penetrant, and orally active dopamine D4 receptor antagonist with a Ki of 0.43 nM. It exhibits weaker affinity for D2 (Ki of 960 nM) and D3 (Ki of 2300 nM) receptors, and shows moderate affinity for 5-HT2 receptors, sigma sites, and α-adrenoceptors[1][2][3].
体内研究
After oral administration to squirrel monkeys, L745870 at a dose of 10 mg/kg causes mild sedation, while more pronounced extrapyramidal motor symptoms, particularly bradykinesia, become evident at 30 mg/kg. Lower doses of L-745870 show no noticeable behavioral effects in monkeys[1].
体外研究
L-745870 effectively counteracts the D4 receptors' ability to suppress agonist-induced stimulation of [35S]-GTPgS binding; it also blocks the inhibition of forskolin-stimulated adenylate cyclase activity in transfected human embryonic kidney (HEK293) and Chinese hamster ovary (CHO) cells; prevents dopamine-induced suppression of Ca2+ currents in transfected GH4C1 pituitary cells; inhibits the activation of cloned G protein-coupled inwardly rectifying K+ channels by D4; and counters dopamine-induced increases in extracellular acidification in transfected cells[1].
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