BMY 7378

• 产品号: S2691
• CAS号: 21102-95-4
• 分子式: C22H33Cl2N3O3
• 分子量: 458.42172
• 保 存: -20°C

产品别名

• 标题: BMY 7378
• IUPAC标准名: 8-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}-8-azaspiro[4.5]decane-7,9-dione dihydrochloride
• IUPAC传统名: 8-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}-8-azaspiro[4.5]decane-7,9-dione dihydrochloride

产品登记号

• CAS号: 21102-95-4

产品性质

• 作用靶点: Serotonin receptor
• 成盐信息: dihydrochloride
• 保存条件: -20°C

产品详细信息

详细说明 (English)

Biological Activity

• Description: BMY 7378 is a multiple inhibitors of α_2C-adrenoceptor and α_1D-adrenoceptor with pK_i of 6.54 and 8.2, respectively.
• Targets:

  α_2C-adrenoceptor

  ;

  α_1D-adrenoceptor

• IC50:

  6.54 (pK_i) ^[1]

  ;

  8.2 (pK_i) ^[2]

• In Vitro: BMY 7378 shows 10-fold selectivity for α_2C-adrenoceptors over other α₂-adrenoceptors with pKi of 6.54. ^[1] BMY 7378 is selective for the α_1D-adrenoceptor subtype (PKi: hamster α_1b-adrenoceptor 6.2, human α_1b-adrenoceptor 7.2; bovine α_1c-adrenoceptor 6.1, human α_1c-adrenoceptor 6.6; rat α_1d-adrenoceptor 8.2, human α_1d-adrenoceptor 9.4 ^[2] BMY 7378 at concentration of 1 nM to 30 nM elicits inhibitory effects in a concentration-dependent manner in the rat dorsal raphe nucleus. ^[3]
• In Vivo: BMY 7378 (pA₂ of 8.67) is approximately 100 times more potent than yohimbine (pA₂ of 6.62) against contractions to noradrenaline in rat aorta. BMY 7378 (pA₂ of 6.48) is approximately 10 times less potent than yohimbine (pA₂ of 7.56) at antagonizing the contractile response to noradrenaline in human saphenous vein (α_2C-adrenoceptor).^[1] BMY 7378 dose dependently (0.25-5 mg/kg s.c.) reduces the undetectable levels forepaw treading and head weaving induced by 8-OH-DPAT (0.75 mg/kg s.c.) in rats. BMY 7378 causes a marked and dose-dependent (0.01-1.0 mg/kg s.c.) decrease of 5-HT release in ventral hippocampus of the anaesthetized rat as detected by brain microdialysis in rats. ^[4]

Combination Therapy

• Description:

  BMY 7378 inhibits 5-HT release induced by 8-OH-DPAT, but this effect is attenuated by pretreatment with the 5-HT1 receptor/beta-adrenoceptor antagonist pindolol (8 mg/kg s.c.), while the effect is not alter by pretreatment with a combination of the beta 1- and beta 2-adrenoceptor antagonists metoprolol (4 mg/kg s.c.) and ICI 118 551 (4 mg/kg s.c.). ^[4]

References

• References: [1] Cleary L, et al. Auton Autacoid Pharmacol, 2005, 25(4), 135-141.
• References: [2] Goetz AS, et al. Eur J Pharmacol, 1995, 272(2-3), R5-6.
• References: [3] Greuel JM, et al. Eur J Pharmacol, 1992, 211(2), 211-219.
• References: [4] Sharp T, et al. Eur J Pharmacol, 1990, 176(3), 331-40.

参考文献

• Cleary L, et al. Auton Autacoid Pharmacol, 2005, 25(4), 135-141.
• Goetz AS, et al. Eur J Pharmacol, 1995, 272(2-3), R5-6.
• Greuel JM, et al. Eur J Pharmacol, 1992, 211(2), 211-219.
• Sharp T, et al. Eur J Pharmacol, 1990, 176(3), 331-40.