A series of anandamide-type compounds were synthesized and studied for
their effect on the intraocular pressure (IOP) of normotensive pigmen
ted rabbits. Each test compound was dissolved in an aqueous 2-hydroxyp
ropyl-beta-cyclodextrin solution and administered (31.25 - 62.5 mu g)
unilaterally to the eye. The most promising anandamides caused a stati
stically significant reduction of IOP in treated eyes, usually precede
d by an initial transient elevation of IOP, compared to saline control
s. In the contralateral untreated eyes, only a marginal or short hypot
ensive response was observed. Indomethacin pre-treatment (12.5 mg, s.c
.) eliminated the IOP response to administered anandamides and arachid
onic acid.