Stampfli H F, Quon C Y
DuPont Merck Pharmaceutical Company, Drug Metabolism and Pharmacokinetics Section, Stine-Haskell Research Center, Newark, DE 19714, USA.
Res Commun Mol Pathol Pharmacol. 1995 Apr;88(1):87-97.
Flestolol, N(1,1-dimethyl-2-ureidocthyl)-2-hydroxy-3-(o-fluorobenzoyloxy++ +) propylamine, (F), is an ester containing an ultra short-acting beta blocker intended for the treatment of myocardial dysfunctions. In vitro incubation of F, procaine, chloroprocaine, and atropine with blood from different New Zealand White (NZW) rabbits resulted in a bimodal distribution (70% fast, 30% slow) of ester hydrolysis rates. Using F as a model substrate, bimodal hydrolysis rates were also observed in NZW rabbit cornea but not aqueous humor, iris-ciliary body complex and ocular tissues of pigmented rabbits. In addition, the bimodal distribution of esterase activity was not observed in blood from rats, dogs, and humans. Incubation of esters at various positions of the phenoxypropanolamine nucleus of beta blockers with NZW rabbit blood indicated structural specificity of the carboxylesterase in terms of unimodal or biomodal distribution of activity. These results strongly suggest that the carboxylesterase in NZW rabbit blood that hydrolyzes F and similar compounds is atropine esterase as described in the literature.
氟司洛尔，N-(1,1-二甲基-2-脲基乙基)-2-羟基-3-(邻氟苯甲酰氧基)丙胺，(F)，是一种含有超短效β受体阻滞剂的酯类药物，用于治疗心肌功能障碍。将F、普鲁卡因、氯普鲁卡因和阿托品与不同新西兰白兔（NZW）的血液进行体外孵育，结果显示酯水解速率呈双峰分布（70%快，30%慢）。以F为模型底物，在NZW兔角膜中也观察到双峰水解速率，但在房水、虹膜睫状体复合体和有色兔的眼组织中未观察到。此外，在大鼠、狗和人类的血液中未观察到酯酶活性的双峰分布。用NZW兔血液孵育β受体阻滞剂苯氧丙醇胺核不同位置的酯类，结果表明羧酸酯酶在活性单峰或双峰分布方面具有结构特异性。这些结果强烈表明，NZW兔血液中水解F及类似化合物的羧酸酯酶是文献中所述的阿托品酯酶。
