BRL-15572 dihydrochloride

SKU: orb1300782

Description

BRL-15572 dihydrochloride is a selective 5-HT1D receptor antagonist (pKi = 7.9) with significant affinity for 5-HT1A and 5-HT2B receptors. This compound is a valuable pharmacological tool used in vitro and in vivo to study serotonin receptor function in neuropharmacology and related disorders.

Research Area

Neuroscience, Pharmacology & Drug Discovery

Key Properties

• CAS Number: 193611-72-2
• MW: 479.87
• Purity: 99.80% (May vary between batches)
• Formula: C₂₅H₂₇ClN₂O·2HCl
• SMILES: Cl.OC(CN1CCN(CC1)c1cccc(Cl)c1)C(c1ccccc1)c1ccccc1
• Target: 5-HT Receptor
• Solubility: DMSO:89 mg/mL (185.47 mM);H2O:< 1 mg/mL (insoluble or slightly soluble);10% DMSO+40% PEG300+5% Tween 80+45% Saline:3.3 mg/mL (6.88 mM);Ethanol:38 mg/mL (79.19 mM)

Bioactivity

• Target IC50:
  5-HT1D:7.9(pKi)|5-HT7:6.3(pKi)|5-HT2A:6.6(pKi)|5-HT1A:7.7(pKi)|5-HT2B:7.4(pKi)
• In Vivo:
  In diabetic pithed rats, administration of the selective 5-HT1D receptor antagonist BRL-15572 (2 mg/kg) does not modify the decreased HR induced by vagal electrical stimulation. The effects of L-694,247 (50 μg/kg), a selective agonist for non-rodent 5-HT1B and 5-HT1D receptors, on the vagally induced bradycardia are not apparent after pretreatment with BRL-15572.
• In Vitro:
  BRL-15572 displays high affinity and selectivity for h5-HT1D receptors. BRL-15572 has 60-fold higher affinity for h5-HT1D than 5-HT1B receptors. BRL-15572 binds to h5-HT1B and h5-HT1D receptors with pKB of less than 6 and 7.1, respectively. BRL-15572 stimulates [35S]GTP γ S binding in both cell lines, with potencies that correlated with their receptor binding affinities in both h5-HT1B and h5-HT1D receptor expressing cell lines. BRL-15572 reveals receptor binding affinities for 5-HT1A, 5-HT1B, 5-HT1E, 5-HT1F, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT6 and 5-HT7 with pKi of 7.7, 6.1, 5.2, 6.0, 6.6, 7.4, 6.2, 5.9 and 6.3, respectively. In the h5-HT1D cell line, both BRL-15572 (1 μM) shifts the 5-HT concentration response curve with pKB of 7.1, respectively. BRL-15572 does have moderately high affinity at human 5-HT1A and 5-HT2B receptors. In human atrial appendages, the electrically evoked tritium overflow is inhibited by 5-HT in a manner susceptible to antagonism by BRL-15572 (300 nM; 23 times Ki at h5-HT1D receptors). The inhibitory effect of 5-HT on the K+-evoked overflow of glutamate is antagonized by the h5-HT1D receptor ligand BRL-15572. BRL-15572 (1 μM) is unable to modify the effect of 5-HT at the autoreceptor regulating [3H]5-HT release. The selective 5-HT1D/1B receptor antagonist BRL 15572 inhibits the effect of the agonist L-694 247.
• Cell Research:
  [35S]GTPγS binding studies. [35S]GTPγS binding studies in CHO cells expressing the h5-HT1B or h5-HT1D receptors are performed. In brief, membranes from 1 × 106 cells are preincubated at 30°C for 30 minutes, in HEPES buffer (HEPES [20 mM], MgCl2 [3 mM], NaCl [100 mM], ascorbate [0.2 mM]), containing GDP (10 μ M), with or without BRL-15572. The reaction is started by the addition of 10 μL of [35S]GTPγS (100 pM, assay concentration) followed by a further 30 minutes incubation at 30°C. Non-specific binding is determined by addition of unlabelled GTPγS (10 μM), prior to the addition of cells. The reaction is stopped by rapid filtration using Whatman GF/B grade filters followed by five washes with ice-cold HEPES buffer. Radioactivity is determined by liquid scintillation spectrometry.(Only for Reference)

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

BRL15572, BRL-15572, BRL15572 dihydrochloride, BRL15572 Dihydrochloride, BRL-15572 Dihydrochloride, BRL15573, BRL-15573, BRL15573 Dihydrochloride, BRL-15573 Dihydrochloride, BRL 15572, BRL 15572 dihydrochloride, BRL 15572 Dihydrochloride, BRL 15573, BRL 15573 dihydrochloride, BRL 15573 Dihydrochloride, 5HT Receptor, 5-HT1A, 5-HT Receptor, 5-HT1D, 5-HT2A, 5-HT2B, 5-hydroxytryptamine Receptor, 5-HT7, 5HTReceptor, inhibit, Inhibitor, h5-HT1D, Serotonin Receptor

Compound Identifiers

PubChem CID

11957475