Ocular hypotensive action of ergoline derivatives in rabbits: effects of sympathectomy and domperidone pretreatment

Abstract

Ergot derivatives, such as bromocriptine, lergotrile and pergolide, are potent dopaminergic agonists in various biological systems. In topical doses ranging from 0.001 to 1% applied unilaterally, each agent produced dose-related ocular hypotension in normal rabbits. Utilizing an intraocular pressure (IOP) recovery rate method (aqueous formation index), each agent was observed to suppress the recovery rate of IOP in normal rabbits. Pretreatment with a prejunctional dopamine receptor antagonist (domperidone) inhibited the ocular hypotensive effect of bromocriptine and pergolide more than that of lergotrile. In rabbits with unilateral superior cervical ganglionectomies, IOP was lowered appreciably less by these compounds in the denervated eyes. These studies indicate that: a) lowering of IOP by these ergot derivatives is dependent, in part, on suppression of sympathetic neuronal activity; b) the most probable sites of action are DA2 receptors on sympathetic nerve endings or in sympathetic ganglia; c) ocular hypotension is produced, in part, by suppressing aqueous humor formation.

The effects of lisuride, terguride and bromocriptine on intraocular pressure (IOP).

“…It is interesting that ergot derivatives reduce IOP in animals (Potter & Burke, 1983;Potter et al, 1984;Potter & Shumate, 1987;Siegel et al, 1987) and in ocular normotensive (Mekki et al, 1983(Mekki et al, , 1984Mekki & Turner, 1985;Geyer et al, 1987a) and hypertensive (Lustig, 1983;Geyer et al, 1987b) human eyes.…”

“…This pharmacological and anatomical evidence, in both animals (Potter et al, 1984) and man (Mekki & Turner, 1985) points to the involvement of dopamine-2 (D2) receptors in the ocular hypotensive effect of ergot derivatives by inhibiting aqueous humour formation (Siegel et al, 1987).…”

“…It has also been shown that the ergot derivatives, bromocriptine, lergotrile, and pergolide produce a dose related ocular hypotension in rabbits and monkeys (Potter & Burke, 1983). Domperidone (a selective D2-receptor antagonist) and sympathectomy inhibited this hypotensive effect (Potter et al, 1984). Recently, cianergoline, another ergot derivative, has been reported to reduce intraocular pressure in rabbits and monkeys (Potter & Shumate, 1987).…”

The effect of a single oral dose of pergolide on intraocular pressure and pupil diameter.

“…This leaves the way open for further investigation of the effect of a topical application of this drug on IOP in-normal and glaucomatous patients to evaluate the usage of this drug for treatment of glaucoma. The ocular hypotensive effect of pergolide is unlikely to be related to its systemic hypotensive effect or through an action on DI-receptors or aadrenoceptors in the eye, as domperidone blocked this effect in rabbits (Potter et al, 1984). Further pharmacological studies, using a selective D2-receptor antagonist, such as domperidone, and utilising tonographic and fluorophotometric methods are desirable to elucidate the mechanism of the ocular hypotensive action of dopaminergic drugs.…”

“…Domperidone (a selective dopamine-2 (D2)-receptor antagonist) and sympathectomy inhibited this effect (Potter et al, 1984). Recently, cianergoline (Potter & Shumate, 1987) and LY-141865 (Potter & Burke, 1988), other ergot derivatives which are relatively selective D2-receptor agonists, have been reported to reduce intraocular pressure (IOP) in rabbits and monkeys.…”