Effects of 2-alkynyladenosine derivatives on intraocular pressure in rabbits.
We evaluated the activities of 2-alkynyladenosine derivatives, relatively selective adenosine A2 receptor agonists, in the intraocular pressure regulation in rabbits. An adenosine A2 receptor agonist 2-[p-(2-carboxyethyl)phenylethylamino]-5'-N-ethylcarboxamidoadenosine (CGS-21680) decreased intraocular pressure, while another A2 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 alpha-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 A2 receptor antagonist 3,7-dimethyl-1-propargylxanthine, but not by an adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropyl xanthine. These findings suggest that 2-alkynyladenosine derivatives may affect intraocular pressure via adenosine A2 receptor, and 2-alkynyladenosine derivative-induced ocular hypotension is due to the increase of outflow facility.
Drug Research Section II, Fukushima Research Laboratories, TOA EIYO LTD, 1 Tanaka, Yuno, Iizaka, Fukushima 960-0280, Japan. konno.takashi@toaeiyo.co.jp
Takashi
T
Konno
Shin-ya
SY
Ohnuma
Kazuhiro
K
Uemoto
Takehiro
T
Uchibori
Akihiko
A
Nagai
Kentaro
K
Kogi
Kazuki
K
Endo
Tomokazu
T
Hosokawa
Norimichi
N
Nakahata
D000241:Adenosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D000287:Administration, Topical; D000480:Alkynes / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000737:chemistry / Q000494:pharmacology*; D002918:Chymotrypsin; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D009798:Ocular Hypertension / Q000139:chemically induced / Q000188:drug therapy; D011817:Rabbits; D013997:Time Factors
D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D000480:Alkynes; D000959:Antihypertensive Agents; D002918:Chymotrypsin; C117608:alpha-chymotrypsin; D000241:Adenosine