Effect of 2-(6-cyano-1-hexyn-1-yl)adenosine on ocular blood flow in rabbits.
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.
Konno
Takashi
T
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
Uchibori
Takehiro
T
Nagai
Akihiko
A
Kogi
Kentaro
K
Nakahata
Norimichi
N
D000241:Adenosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D002110:Caffeine / Q000031:analogs & derivatives / Q000494:pharmacology; D005123:Eye / Q000098:blood supply* / Q000378:metabolism; D005415:Flavins / Q000494:pharmacology; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects; D012171:Retinal Vessels / Q000187:drug effects* / Q000378:metabolism; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D014970:Xanthines / Q000494:pharmacology
C504088:2-(6-cyano-1-hexyn-1-yl)adenosine; D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D005415:Flavins; D014665:Vasodilator Agents; D014970:Xanthines; C081320:8-(3-chlorostyryl)caffeine; D002110:Caffeine; C008173:isoalloxazine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine