Dopamine (DA1 and DA2) receptors have been demonstrated functionally in the anterior segment of the eye. Previous results have indicated that
bromocriptine, a relatively selective DA2 agonist, can lower intraocular pressure (IOP) in laboratory animals as well as in normal and glaucomatous humans. Other
ergoline derivatives (
pergolide,
lergotrile, LY141865) have also been demonstrated to lower IOP in laboratory animals.
Cianergoline, a new
ergoline derivative, was tested for: 1) ocular hypotensive activity in normal and sympathectomized (SX) rabbits and in normal capuchin monkeys, 2) inhibition of induced
ocular hypertension by waterloading in rabbits and 3) suppression of contractions of the cat nictitating membrane (CNM) elicited by electrical stimulation of sympathetic nerves and by intraarterial (i.a.) injection of
norepinephrine (NE). Topically administered
cianergoline (0.022-0.22 mg) produced dose-related, unilateral
ocular hypotension in normal but not in SX rabbits. In addition,
cianergoline (0.5 mg) produced a slight reduction of IOP in capuchin monkeys. There were no significant effects on iris function in rabbits, however,
miosis did occur in the monkeys.
Cianergoline (0.22mg) suppressed
ocular hypertension induced by waterloading in rabbits, and this effect was antagonized by
metoclopramide, a relatively selective DA2 antagonist.
Cianergoline (1-333 micrograms, i.a.) also produced dose-related inhibition of neuronally mediated contractions of the CNM.
Cianergoline inhibited low frequency (2 & 4 Hz) contractile responses of the CNM more than high frequency (6 & 8 Hz) responses. Contractions of the CNM caused by i.a. NE were also inhibited by higher concentrations of
cianergoline. These data demonstrate that
cianergoline, like
bromocriptine, can lower IOP and that the predominant mechanism involves inhibition of sympathetic neuronal function at prejunctional (DA2) and postjunctional (alpha 1)
adrenoceptors.