• 主页
  • 查找结果
  • The in vitro and in vivo profile of aclidinium bromide in comparison with glycopyrronium bromide.

The in vitro and in vivo profile of aclidinium bromide in comparison with glycopyrronium bromide.

Pulmonary pharmacology & therapeutics (2014-06-15)
Amadeu Gavaldà, Israel Ramos, Carla Carcasona, Elena Calama, Raquel Otal, José Luis Montero, Sonia Sentellas, Monica Aparici, Dolors Vilella, Joan Alberti, Jorge Beleta, Montserrat Miralpeix
摘要

This study characterised the in vitro and in vivo profiles of two novel long-acting muscarinic antagonists, aclidinium bromide and glycopyrronium bromide, using tiotropium bromide and ipratropium bromide as comparators. All four antagonists had high affinity for the five muscarinic receptor sub-types (M1-M5); aclidinium had comparable affinity to tiotropium but higher affinity than glycopyrronium and ipratropium for all receptors. Glycopyrronium dissociated faster from recombinant M3 receptors than aclidinium and tiotropium but more slowly than ipratropium; all four compounds dissociated more rapidly from M2 receptors than from M3 receptors. In vitro, aclidinium, glycopyrronium and tiotropium had a long duration of action at native M3 receptors (>8 h versus 42 min for ipratropium). In vivo, all compounds were equi-potent at reversing acetylcholine-induced bronchoconstriction. Aclidinium, glycopyrronium and ipratropium had a faster onset of bronchodilator action than tiotropium. Aclidinium had a longer duration of action than glycopyronnium (time to 50% recovery of effect [t½ offset] = 29 h and 13 h, respectively); these compare with a t½ offset of 64 h and 8 h for tiotropium and ipratropium, respectively. Aclidinium was less potent than glycopyrronium and tiotropium at inhibiting salivation in conscious rats (dose required to produce half-maximal effect [ED50] = 38, 0.74 and 0.88 μg/kg, respectively) and was more rapidly hydrolysed in rat, guinea pig and human plasma compared with glycopyrronium or tiotropium. These results indicate that while aclidinium and glycopyrronium are both potent antagonists at muscarinic receptors with similar kinetic selectivity for M3 receptors versus M2, aclidinium has a longer dissociation half-life at M3 receptors and a longer duration of bronchodilator action in vivo than glycopyrronium. The rapid plasma hydrolysis of aclidinium, coupled to its kinetic selectivity, may confer a reduced propensity for systemic anticholinergic side effects with aclidinium versus glycopyrronium and tiotropium.

材料
货号
品牌
产品描述

Sigma-Aldrich
乙腈, suitable for HPLC, gradient grade, ≥99.9%
Sigma-Aldrich
乙腈, anhydrous, 99.8%
Sigma-Aldrich
乙腈, HPLC Plus, ≥99.9%
Sigma-Aldrich
甲酸, reagent grade, ≥95%
Sigma-Aldrich
氨 溶液, 7 N in methanol
Sigma-Aldrich
甲酸, puriss. p.a., ACS reagent, reag. Ph. Eur., ≥98%
Sigma-Aldrich
乙腈, suitable for HPLC, gradient grade, ≥99.9%
Sigma-Aldrich
甲酸, ACS reagent, ≥96%
Sigma-Aldrich
乙腈 溶液, contains 0.1 % (v/v) trifluoroacetic acid, suitable for HPLC
Sigma-Aldrich
氨, anhydrous, ≥99.98%
Sigma-Aldrich
甲酸, puriss., meets analytical specifications of DAC, FCC, 98.0-100%
Sigma-Aldrich
乙腈, ACS reagent, ≥99.5%
Sigma-Aldrich
乙腈, suitable for HPLC-GC, ≥99.8% (GC)
Sigma-Aldrich
甲酸, ACS reagent, ≥88%
Sigma-Aldrich
氨 溶液, 2.0 M in ethanol
Sigma-Aldrich
乙腈 溶液, contains 0.1 % (v/v) formic acid, suitable for HPLC
Sigma-Aldrich
氨 溶液, 0.4 M in THF
Sigma-Aldrich
卡巴胆碱, ≥98% (titration), crystalline
Sigma-Aldrich
氨 溶液, 0.4 M in dioxane
Sigma-Aldrich
氨 溶液, 2.0 M in methanol
Sigma-Aldrich
乙腈, HPLC Plus, ≥99.9%, poly-coated bottles
Supelco
乙腈, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
硫酸阿托品, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
甲酸, ≥95%, FCC, FG
Sigma-Aldrich
2,6-二异丙基苯酚, 97%
Sigma-Aldrich
阿托品 硫酸盐 一水合物, ≥97% (TLC), crystalline
Sigma-Aldrich
氨 溶液, 4 M in methanol
Sigma-Aldrich
甲苯噻嗪, ≥99%
Sigma-Aldrich
甲酸 溶液, BioUltra, 1.0 M in H2O
Sigma-Aldrich
乙腈, biotech. grade, ≥99.93%