Dopamine (DA) and three methylated analogs (N-
methyldopamine,
NMDA;
N, N- dimethyldopamine , DMDA ;
N,N-di-n- propyldopamine ,
DPDA) were examined for effects on intraocular pressure (IOP) and pupil diameter (PD) in normal rabbits, sympathectomized (SX) rabbits and rabbits with transected extraocular muscles ( EOMX ) following
topical administration. In normal rabbits, the predominant effect of DA,
NMDA and DMDA was transient, unilateral
ocular hypertension with minimal effects on PD. In contrast,
DPDA produced bilateral
ocular hypotension in normal rabbits. DA and
NMDA did not produced
ocular hypertension in EOMX rabbits indicative of an involvement of extraocular muscles in normal rabbits. In SX rabbits,
NMDA produced
mydriasis and exaggerated
ocular hypertension followed by significant
ocular hypotension; the ocular hypotensive phase was antagonized by
timolol pretreatment. The ocular hypotensive activity of
DPDA seen in normal rabbits was absent in SX rabbits suggestive of a neuronal site of action for
DPDA.
DPDA inhibited contraction of the cat nictitating membrane elicited by stimulation of pre- and postganglionic sympathetic nerves. This effect was antagonized by a
dopamine (DA2) antagonist
metoclopramide, indicative of a prejunctional site of action.
NMDA and DA suppressed
ocular hypertension induced by water loading. Only
NMDA depressed the IOP recovery rate in response to infusion of hypertonic saline indicating suppression of aqueous humor formation. These results suggest that DA,
NMDA and DMDA produce an initial
ocular hypertension by contracting extraocular muscles.
Timolol antagonized the ocular hypotensive effect of
NMDA in SX rabbits indicating that this response is, in part, a function of beta-
adrenoceptor stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)