antagonist).Thymoxamine can also be used to reverse phenylephrine mydriasis,282 alleviate mydriasis after penetrating keratoplasty,260 reposition an iris-supported intraocular lens, and treat lid retraction in conditions such as thyroid eye disease.283 The drug can cause stinging, conjunctival hyperemia, ptosis, and epistaxis.272

Dapiprazole

Dapiprazole (Rev-Eyes™, Storz Ophthalmics, a division of Bausch & Lomb, Rochester, NY) is an -adrenergic antagonist clinically used for the reversal of pharmacologically-induced mydriasis.284,285 It has little direct effect on IOP in open-angle glaucoma. Dapiprazole has been used in patients with pigmentary glaucoma as a way of lifting the peripheral iris off the zonules without inducing accommodative spasm. Long-term dapiprazole seems to lead to improved outflow facility286 and reduced exercise-induced IOP elevation.287 The clinical significance of these observations has not yet been determined, but clearly further studies are indicated. At the time of publication, Bausch & Lomb has ceased manufacture and marketing of this agent.

Bunazosin

Bunazosin is a topical 1-selective adrenergic antagonist. In a 0.3%

solution, it lowers IOP in normal volunteers and in glaucoma patients.288,289 Its mechanism of action appears to be to increase

uveoscleral outflow, because there is no effect on aqueous inflow, outflow facility, episcleral venous pressure, or blood–aqueous barrier, perhaps by causing relaxation of the ciliary muscle rather than

upregulation of matrix metalloproteinases as the prostanoids do.290,291 As might be expected, conjunctival hyperemia, miosis,

and ptosis are side effects. In one study, miosis persisted for 24 hours after a single dose. It is additive to both prostanoids and-blockers.87 Bunazosin has not reached mainstream treatment status yet but may do so in the future.

Prazosin

Prazosin is a selective 1-adrenergic antagonist. The drug reduces

aqueous humor formation and IOP in animal eyes when administered topically in concentrations of 0.001–0.1%.292,293 Its effect on

aqueous humor production may be mediated in part by a decrease in blood pressure.

Others

Other -adrenergic antagonists, including dibenzylchlorethamine,

phentolamine, phenoxybenzamine, and corynanthine, lower IOP in rabbit eyes when administered topically or systemically.284,294–295

Some of these drugs may reduce IOP through non-adrenergic mechanisms.

Combined 1- and -adrenergic antagonists

Several combined 1- and -adrenergic antagonists have been developed. Some such as carvedilol are used clinically as anti­ hypertensive agents and in congestive heart failure. Two, amosulalol and napradilol, have been tried as topical antiglaucoma agents.

Amosulalol 0.1% reduces IOP and increases optic nerve head blood flow in rabbits.297,298 The mechanism of action appears to be both

a decrease in aqueous production and an increase in uveoscleral outflow. Presumably the former comes from the -blocking aspect and the latter from the 1-blocking aspect. Napradilol 0.25% topically also reduces IOP via similar mechanisms.299 Nipradilol also acts as a neuroprotectant in vitro for retinal ganglion cells through a nitric oxide mechanism. These agents have an antiangina effect purportedly through a similar mechanism.

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