In vitro potential measurement, anaesthetic and antimicrobial effects as indicators of beta-blocker toxicity of the cornea.
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.
Himber
J
J
Andermann
G
G
Erhart
M
M
Leclerc
G
G
Bouzoubaa
M
M
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D000900:Anti-Bacterial Agents; D002417:Cattle; D003315:Cornea / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011817:Rabbits; D012995:Solubility; D013999:Timolol / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D000900:Anti-Bacterial Agents; D011412:Propanolamines; C045888:falintolol; D013999:Timolol; C046146:O-(2-hydroxy-3-(tert-butylamino)propyl)-3,3,5-trimethylcyclohexanone oxime; D011433:Propranolol