L-745870 trihydrochloride

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

L-745870 triHClide 是一种高效、选择性 D4 多巴胺受体拮抗剂。 L-745870 triHClide 对 5-HT2 受体、σ 位点和 α-肾上腺素受体具有中等亲和力，对 D2 和 D3 受体具有较弱的亲和力。

L-745870 trihydrochloride is a highly potent and selective D4 dopamine receptor antagonist. L-745870 trihydrochloride exhibits moderate affinity for 5-HT2 receptors, sigma sites and α-adrenoceptors and shows weaker affinity for D2 and D3 receptors.(In Vitro):L-745870 antagonizes the ability of D4 receptors to inhibit agonist-induced [35S]-GTPgS binding stimulation; blocks forskolin-stimulated adenocarcinoma in transfected human embryonic kidney (HEK293) and Chinese hamster ovary (CHO) cells Inhibition of pyridyl cyclase activity; blockade of dopamine-induced inhibition of Ca2+ currents in transfected GH4C1 pituitary cells; inhibition of D4 activation of cloned G protein-coupled inwardly rectifying K+ channels; and antagonism of dopamine-induced inhibition of transfected cells Stimulation of extracellular acidification .(In Vivo):L-745870 has favorable pharmacokinetic properties in both rats and monkeys, and shows excellent brain permeability and a high brain-to-plasma ratio in rats . L-745870 (10 mg/kg p.o.) at 30 mg/kg caused mild sedation and extrapyramidal motor symptoms, especially bradykinesia, following oral administration to squirrel monkeys. Lower doses of L-745870 had no apparent behavioral effects in monkeys .

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.

L-745870 has good pharmacokinetic properties (20-60% oral bioavailability and plasma t1/2 2.1-2.8 hours) in both rat and monkey, and excellent brain penetration with high brain to plasma ratios in rat.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.

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GPCR/G Protein

Dopamine Receptor

Syk

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866021-03-6

436.2

C18H22Cl4N4

>98% (HPLC)

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Cl.Cl.Cl.Clc1ccc(cc1)N1CCN(Cc2c[nH]c3ncccc23)CC1

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(-20℃)

With Ice Pack

≥ 2 years