Effect of 2-(6-cyano-1-hexyn-1-yl)adenosine on ocular blood flow in rabbits |
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Authors: | Konno Takashi Uchibori Takehiro Nagai Akihiko Kogi Kentaro Nakahata Norimichi |
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Institution: | Drug Research Section II, Fukushima Research Laboratories, R&D Department, Toa Eiyo Ltd., 1 Tanaka, Yuno, Iizaka, Fukushima 960-0280, Japan. konno.takashi@toaeiyo.co.jp |
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Abstract: | Previously, we reported that a relatively selective adenosine A(2A) receptor agonist 2-(6-cyano-1-hexyn-1-yl)adenosine (2-CN-Ado) elicited ocular hypotension in rabbits (Journal of Pharmacological Sciences 2005;97:501-509). In the present study, we investigated the effect of 2-CN-Ado on ocular blood flow in rabbit eyes. An intravitreal injection of 2-CN-Ado increased ocular blood flow, measured by a non-contact laser flowmeter. 2-CN-Ado-induced increase in ocular blood flow was accompanied with the retinal vasodilation. The increase in ocular blood flow was inhibited by an adenosine A(2A) receptor antagonist 1,3,7-trimethyl-8-(3-chlorostyryl)xanthine, but not by an adenosine A(2B) receptor antagonist alloxazine or an adenosine A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine. The repetitive applications of topical 2-CN-Ado twice a day for 7 days produced a persistent increase in ocular blood flow with ocular hypotension. These results suggest that 2-CN-Ado increases the ocular blood flow mainly via adenosine A(2A) receptor, and that the topical application of 2-CN-Ado for several days not only increases the ocular blood flow but also prolong ocular hypotension, indicating that 2-CN-Ado may be a useful lead compound for the treatment of ischemic retinal diseases such as glaucoma. |
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Keywords: | 2-Alkynyladenosine derivatives Adenosine A2A receptor Ocular blood flow Intraocular pressure |
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