title: Fadolmidine-induced ocular hypotension in normotensive rabbits.
abstract: Fadolmidine, a novel selective alpha2-adrenoceptor agonist, was evaluated for its efficacy to lower intraocular pressure in normotensive rabbits (n=5-6). The dose-response profile between 0.004 microg and 12.5 microg of fadolmidine was determined. The effect of pH on the partition of fadolmidine was studied in order to select an optimal pH for topical fadolmidine administration. After topical administration, fadolmidine significantly lowered the intraocular pressure in normotensive rabbits. The onset of action was immediate, with no initial increase in intraocular pressure. A significant decrease in intraocular pressure was already observed at 1 h after dosing. The maximum decrease in intraocular pressure was observed after a 2.5 microg dose of fadolmidine in both eyes at 2 h after dosing. The mean maximum decrease in the treated and untreated eye was 6.4 mmHg and 3.9 mmHg, respectively. In conclusion, fadolmidine is a potent intraocular pressure lowering agent. In addition, fadolmidine does not cause a significant initial increase in intraocular pressure. Because of the strong dependence of the distribution coefficient on pH, the pH of the administered solution is important, with physiological pH being optimal in this respect.
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kuopio, PO Box 1627, FIN 70211, Kuopio, Finland. jouko.savolainen@uku.fi
authors.forename: Jouko
authors.initials: J
authors.lastname: Savolainen
authors.forename: Riku
authors.initials: R
authors.lastname: Niemi
authors.forename: Antti
authors.initials: A
authors.lastname: Mäntylä
authors.forename: Juhani
authors.initials: J
authors.lastname: Huuskonen
authors.forename: Tomi
authors.initials: T
authors.lastname: Järvinen
mesh_terms: D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005387:Finland; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D007189:Indans / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D007429:Intraocular Pressure / Q000187:drug effects / Q000502:physiology; D008297:Male; D015814:Ocular Hypotension / Q000139:chemically induced*; D011817:Rabbits
chemical_list: D007093:Imidazoles; D007189:Indans; C400294:radolmidine