Himber J, Andermann G, Erhart M, Leclerc G, Bouzoubaa M
Methods Find Exp Clin Pharmacol. 1985 Apr;7(4):195-201.
Three tests were utilized to determine and compare the toxicity of timolol, propranolol and two new aliphatic and alicyclic oxime ethers with beta-blocking activity (falintolol and compound POS 7). Effects on the electrical potential difference across the in vitro bovine corneal epithelium. Local anaesthesia on in vivo rabbit cornea. Antimicrobial activity on bacterial and fungal suspensions. In addition, partition coefficients were determined as physicochemical properties of the drugs. Falintolol, as well as timolol produced a minor change in electrophysiology at clinical concentration. They had neither local anaesthetic, nor antimicrobial effects. Conversely, propranolol and compound POS 7 showed acute corneal toxicity in the present models. It was concluded that changes in the potential difference across a perfused cornea in vitro, local anaesthesia and bacterial inhibition, might be a demonstration of the cytotoxicity of certain topical agents in terms of acute eye tissue reaction. They might represent a valuable model for the acute corneal toxicity evaluation of topical beta-blockers.
采用三项测试来确定和比较噻吗洛尔、普萘洛尔以及两种具有β受体阻断活性的新型脂肪族和脂环族肟醚（法林洛尔和化合物POS 7）的毒性。对体外牛角膜上皮跨膜电位差的影响。对体内兔角膜的局部麻醉作用。对细菌和真菌悬液的抗菌活性。此外，测定了分配系数作为药物的物理化学性质。法林洛尔以及噻吗洛尔在临床浓度下对电生理学产生轻微变化。它们既无局部麻醉作用，也无抗菌作用。相反，普萘洛尔和化合物POS 7在当前模型中表现出急性角膜毒性。得出的结论是，体外灌注角膜跨膜电位差的变化、局部麻醉作用和细菌抑制作用，可能是某些局部用药在急性眼组织反应方面细胞毒性的一种表现。它们可能是局部β受体阻滞剂急性角膜毒性评估的一个有价值的模型。
