Ocular and cardiac beta-antagonism by timolol prodrugs, timolol and levobunolol.
Topically applied O-butyryl timolol, O-pivaloyl timolol and levobunolol (0.25 micrograms) antagonized isoproterenol-induced ocular hypotension for 8 hrs whereas timolol (0.25 micrograms) was shorter acting (4 hrs). Timolol (25 micrograms) produced greater antagonism of isoproterenol-induced tachycardia than did O-butyryl and O-pivaloyl timolol (25 micrograms). These results suggest that, at similar doses, O-butyryl and O-pivaloyl timolol produce high concentrations of timolol in ocular tissues and undergo redistribution more slowly into the systemic circulation than does topical timolol. Under certain circumstances, prodrugs may provide a mechanism for increasing selectivity and extending the duration of action in the target organ as well as decreasing systemic effects.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D005123:Eye / Q000187:drug effects*; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007429:Intraocular Pressure / Q000187:drug effects; D007545:Isoproterenol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002040:Levobunolol / Q000494:pharmacology*; D008297:Male; D011355:Prodrugs / Q000494:pharmacology*; D011817:Rabbits; D013999:Timolol / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D011355:Prodrugs; D013999:Timolol; D002040:Levobunolol; D007545:Isoproterenol