L-745870 hydrochloride

SKU: orb1309502

Description

L-745870 hydrochloride

Research Area

Neuroscience, Pharmacology & Drug Discovery

Key Properties

• CAS Number: 1173023-36-3
• MW: 363.28
• Purity: 97.36%
• Formula: C₁₈H₂₀Cl₂N₄
• SMILES: Cl.Clc1ccc(cc1)N1CCN(Cc2c[nH]c3ncccc23)CC1
• Target: Dopamine Receptor
• Solubility: DMSO:55 mg/mL (151.4 mM);0.1 M HCL:20 mg/mL (55.05 mM)

Bioactivity

• Target IC50:
  D2 receptor (human):960 nM(Ki)|D3 receptor (human):2300 nM(Ki)|D4 receptor (human):0.43 nM(Ki)
• In Vivo:
  L-745870 exhibits favorable pharmacokinetic properties (20-60% oral bioavailability and plasma t1/2 of 2.1-2.8 hours) in both rats and monkeys, with excellent brain penetration and high brain-to-plasma ratios in rats. Evaluation of L-745870 in surrogate marker assays indicates that it is readily available for biological activity in the brain and at doses of 5 to 60 mg/kg p.o., it would occupy 50% of D4 receptors in the brain. L-745870 does not affect apomorphine-induced stereotypy in rats but induces catalepsy in mice at a high dose of 100 mg/kg p.o., likely due to D2 receptor occupancy. Higher doses of L-745870 are anticipated to cause extrapyramidal symptoms in primates as these CNS levels would antagonize D2 receptors. In squirrel monkeys, L-745870 (10 mg/kg p.o.) induces mild sedation and at 30 mg/kg, it causes noticeable extrapyramidal motor symptoms, notably bradykinesia.
• In Vitro:
  In vitro pharmacological studies revealed that L-745870 is an antagonist at human D4 receptors, in that L-745870 antagonized the ability of D4 receptors to inhibit agonist-induced stimulation of [35S]-GTPgS binding, blocked the inhibition of forskolin-stimulated adenylate cyclase activity in transfected human embryonic kidney (HEK293) and Chinese hamster ovary (CHO) cells, blocked dopamine-induced inhibition of Ca2+ currents in transfected GH4C1 pituitary cells, inhibited D4 activation of cloned G protein-coupled inwardly rectifying K+ channels, and antagonized dopamine-induced stimulation of extracellular acidification in transfected cells.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Dopamine Receptor, dopamine, DopamineReceptor, brain, Inhibitor, L745870, L-745870, L745870 Hydrochloride, L745870 hydrochloride, L-745870 Hydrochloride, Human, human D2 receptor, human D3 receptor, human D4 receptor, Human dopamine D2 receptor, Human dopamine D3 receptor, Human dopamine D4 receptor, inhibit, L 745870, L 745870 Hydrochloride, L 745870 hydrochloride, neuroleptics, receptor, penetration

Compound Identifiers

PubChem CID

11957618