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Abstract #8935 Published in IGR 5-2
A novel D2 dopaminergic and α2 adrenoceptor receptor agonist induces substantial and prolonged IOP decrease in normotensive rabbits
Savolainen J; Rautio J; Razzetti R; Jarvinen TJournal of Pharmacy and Pharmacology 2003; 55: 789-794
The effects of a novel and selective D2 dopaminergic/α2 adrenoceptor agonist, CHF1035, and its metabolite CHF1024 on intraocular pressure (IOP) were determined in rabbits. Because CHF1035 is a mixture of two enantiomers, CHF1800 (+) and CHF1810 (-), pure enantiomers were also studied to determine possible differences in IOP decreasing ability depending on the stereochemistry of the molecule. CHF1035, CHF1800 (+), CHF1810 (-), CHF1024, brimonidine and 0.9% NaCl were administered topically to rabbits and IOP was then measured at fixed time intervals. The dose response profile (0.01-1.0% w/v) was determined for CHF1035. CHF1035 and its metabolite CHF1024 significantly lowered IOP in the treated eyes. CHF1035 showed a maximum IOP decrease (7.6 ± 1.5 mmHg) five hours post-dosing, whereas the metabolite CHF1024 showed a maximum decrease in IOP (7.0 ± 0.8 mmHg) three hours post-dosing. The maximum IOP decrease produced by CHF1035 in the treated eye was comparable with that produced by brimonidine (7.8 ± 0.9 mmHg), but CHF1035 had a significantly longer duration of action. Unlike brimonidine, CHF1035 and CHF1024 did not decrease IOP in the untreated eye. CHF1810 (-) lowered the IOP more than CHF1800 (+). No irritation, evaluated as eyelid closure, was observed after topical administration of any of the compounds. Only in the case of CHF1035 1% solution, two rabbits out of six closed the eye for 30-45 seconds. In conclusion, CHF1035 and its metabolite CHF1024 significantly decreased the IOP in rabbits, and are potential novel IOP lowering agents. Especially, CHF1035 produced a substantial decrease in IOP for a prolonged period of time, and thus may prove useful in glaucoma therapy.
Dr. J. Savolainen, Department of Pharmaceutical Chemistry, University of Kuopio, P.O. Box 1627, FIN 70211 Kuopio, Finland. jouko.savolainen@uku.fi
Classification:
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
