Ocular hypotensive effects of anti-glaucoma agents in mice.
OBJECTIVE
To evaluate the ocular hypotensive effects induced by topical application of anti-glaucoma agents in mice.


METHODS
Representative drugs (latanoprost and tafluprost [for prostanoid FP receptor agonists], timolol [for beta-adrenoceptor antagonists], dipivefrin [for alphabeta-adrenoceptor agonists], dorzolamide [for carbonic anhydrase inhibitors], pilocarpine [for muscarinic receptor agonists], bunazosin [for alpha(1)-adrenoceptor antagonists], or brimonidine [for alpha(2)-adrenoceptor agonists]) were used as anti-glaucoma agents; each one being topically applied once in a given male ddY mouse. Intraocular pressure (IOP) was measured using the microneedle method under general anesthesia. IOP was measured before, and at 1, 2, 3, and 4 h after administration of each drug. The contralateral eyes were untreated. At the each time point, the induced IOP reduction was evaluated by calculating the difference in IOP between the treated and untreated eyes in one and the same mouse.


RESULTS
All of the evaluated anti-glaucoma agents reduced IOP in mice. The 2 prostanoid FP receptor agonists, the beta-adrenoceptor antagonist, and the alphabeta-adrenoceptor agonist began significantly to reduce IOP 2 h after their administration, and mostly induced a long-lasting IOP reduction. The alpha(1)-adrenoceptor antagonist, the alpha(2)-adrenoceptor agonist, the muscarinic receptor agonist, and the carbonic anhydrase inhibitor began reducing the IOP within 1 h after their administration, but their effects waned fairly quickly (the IOP reductions being lost by 3 h after their administration). Concomitant administration of timolol and tafluprost or of dorzolamide and tafluprost induced a significantly greater IOP reduction than that induced by either of the individual components.


CONCLUSIONS
In this study, all the anti-glaucoma agents tested had apparent ocular hypotensive effects in mice. Our data suggest that the mouse may be a useful animal for the evaluation of the pharmacological effects of agents with various anti-glaucoma mechanisms, and for the evaluation of the enhanced ocular hypotensive effects that may be induced by the concomitant use of 2 anti-glaucoma agents.
Research and Development Center, Santen Pharmaceutical Co. Ltd., Nara, Japan. takahiro.akaishi@santen.co.jp
Takahiro
T
Akaishi
Noriko
N
Odani-Kawabata
Naruhiro
N
Ishida
Masatsugu
M
Nakamura
D000287:Administration, Topical; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005901:Glaucoma / Q000188:drug therapy*; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D023421:Models, Animal; D009883:Ophthalmic Solutions
D000959:Antihypertensive Agents; D009883:Ophthalmic Solutions