Cianergoline Lowers Intraocular Pressure in Rabbits and Monkeys and Inhibits Contraction of the Cat Nictitans by Suppressing Sympathetic Neuronal Function

ABSTRACT

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 (0.022-0.22mg) produced dose-related, unilateral ocular hypotension in normal but not in SX rabbits. In addition, cianergoline (0.5mg) 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 (1-333μg, 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 (α₁) adrenoceptors.