Glaucoma is a white matter disease where the ganglion cell axons situated in the optic nerve head are insulted in some way. Significantly, sodium channel blockers, including local anaesthetics, offer protection to anoxia-induced injury of rat optic nerves. Calcium channel blockers appear effective at attenuating anoxia-induced injury to neurones but not to axons. All tested b-blockers used in ophthalmology are also calcium channel blockers with betaxolol being the most efficacious. Since certain b-adrenoceptor antagonists possess local anaesthetic activity, studies were undertaken to examine whether the b-blockers used to treat glaucoma interact directly with the sodium channel.
Two major binding sites exist on the sodium channel: neurotoxin sites 1 and 2. Betaxolol had the greatest affinity for site 2 (IC50 value 9.8mM) followed by levobunolol (48.0mM), carteolol (54.9mM) and timolol (79.7mM). None of the substances had an affinity for site 1. Interaction with site 1 would suggest the substance to have toxic properties. Moreover, betaxolol was most efficacious in inhibiting the veratridine-stimulated sodium influx into nerve endings with an IC50 value of 28mM and levobunolol, carteolol and timolol were significantly less effective.
These studies show that of the b-blockers used in ophthalmology, betaxolol interacts most effectively with site 2 of sodium channel and inhibits sodium influx into axons and can therefore potentially ameliorate damage to the ganglion cell axons as occurs in glaucoma.
For details see: Chidlow G, Melena J & Osborne NN (2000) British Journal of Pharmacology 130, 759-766.