Effects of 2-alkynyladenosine derivatives on intraocular pressure in rabbits
2004
Abstract We evaluated the activities of 2-alkynyladenosine derivatives, relatively selective adenosine A 2 receptor agonists, in the intraocular pressure regulation in rabbits. An adenosine A 2 receptor agonist 2-[ p -(2-carboxyethyl)phenylethylamino]-5′- N -ethylcarboxamidoadenosine (CGS-21680) decreased intraocular pressure, while another A 2 receptor agonist 2-(phenylamino)adenosine transiently increased it. The first group of 2-alkynyladenosine derivatives (1-hexyn-1-yl derivatives) caused a transient increase followed by decrease in intraocular pressure, while the second group (1-octyn-1-yl and 6-cyano-1-hexyn-1-yl derivatives) only decreased it. The second group is also effective in the ocular hypertensive models induced by water-loading and α-chymotrypsin. The outflow facility was increased by a 1-octyn-1-yl derivative. Both increase and decrease in intraocular pressure induced by 2-alkynyladenosine derivatives were inhibited by an adenosine A 2 receptor antagonist 3,7-dimethyl-1-propargylxanthine, but not by an adenosine A 1 receptor antagonist 8-cyclopentyl-1,3-dipropyl xanthine. These findings suggest that 2-alkynyladenosine derivatives may affect intraocular pressure via adenosine A 2 receptor, and 2-alkynyladenosine derivative-induced ocular hypotension is due to the increase of outflow facility.
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