product name BRL-15572
Description: BRL-15572 is a 5-HT1D receptor antagonist with pKi of 7.9, also shows a considerable affinity at 5-HT1A and 5-HT2B receptors, exhibiting 60-fold selectivity over 5-HT1B receptor. In the in vitro binding assay, BRL-15572 shows 60-fold higher affinity for human 5-HT1D receptor than for h5-HT1B receptor. However, it also has moderately high affinity at both human 5-HT1A and human 5-HT2B receptors. It limits the use of BRL-15572 as a pharmacological tool in systems.
References: Naunyn Schmiedebergs Arch Pharmacol. 1997;356:312-20; Clin Exp Pharmacol Physiol. 2007;34:1199-206.
479.87
Formula
C25H27ClN2O.2HCl
CAS No.
193611-72-2
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 96 mg/mL (200.1 mM)
Water: <1 mg/mL
Ethanol: 40 mg/mL (83.4 mM)
Solubility (In vivo)
30% Propylene glycol, 5% Tween 80, 65% D5W: 20 mg/mL
Synonyms
other peoduct :
| In Vitro |
In vitro activity: 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. Kinase Assay: Cell Assay: [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. |
|---|---|
| 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. |
| Animal model | Male Wistar rats with diabetes |
| Formulation & Dosage | Dissolved in 20% propylene glycol; 1 mg/kg, 2 mg/kg; i.v. injection |
| References | Naunyn Schmiedebergs Arch Pharmacol. 1997 Sep;356(3):312-20; Clin Exp Pharmacol Physiol. 2007 Nov;34(11):1199-206. |
