产品分类

靶点

5-HT_1D

IC50

7.9 (pK_i)

体外研究

BRL-15572 displays high affinity and selectivity for h5-HT_1D receptors. BRL-15572 has 60-fold higher affinity for h5-HT_1D than 5-HT_1B receptors. BRL-15572 binds to h5-HT_1B and h5-HT_1D 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-HT_1B and h5-HT_1Dreceptor expressing cell lines. BRL-15572 reveals receptor binding affinities for 5-HT_1A, 5-HT_1B, 5-HT_1E, 5-HT_1F, 5-HT_2A, 5-HT_2B, 5-HT_2C, 5-HT₆ and 5-HT₇ with pK_i of 7.7, 6.1, 5.2, 6.0, 6.6, 7.4, 6.2, 5.9 and 6.3, respectively. In the h5-HT_1D cell line, both BRL-15572 (1 μM) shifts the 5-HT concentration response curve with pK_B of 7.1, respectively. BRL-15572 does have moderately high affinity at human 5-HT_1A and 5-HT_2B 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-HT_1D 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.

体内研究

In diabetic pithed rats, administration of the selective 5-HT_1D 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-HT_1B and 5-HT_1D receptors, on the vagally induced bradycardia are not apparent after pretreatment with BRL-15572.

溶解性

DMSO 96 mg/mL，水 <1 mg/mL，乙醇 40 mg/mL

稳定性

2年 -20°C粉状，6月-80°C溶于DMSO

特征

BRL 15572 is a selective 5-HT_1D/1B receptor antagonist.