Topical rivastigmine, a selective acetylcholinesterase inhibitor, lowers intraocular pressure in rabbits

Non-selective acetylcholinesterase (AChE) inhibitors are known hypotensive agents. The purpose of the present investigation was carried out to ascerta in whether rivastigmine, a selective carbamate-type inhibitor of AChE, whic h inhibits selectively an isoform of this enzyme found almost exclusively i n the central nervous system, is able to depress the intraocular pressure ( IOP) in normotensive rabbits. IOP was monitored with a TonoPen XL in conscious adult rabbits before and h ourly up to g hr after administration of the drug. Baseline measurements wi thout treatment and after one single topical application of rivastigmine [1 % (n=8); 2% (n=4); and 5% (n=6)] to the right eye and of the vehicle alone to the left one were performed. Rivastigmine reduced the IOP of treated eyes significantly (p<0.05) in a do se-independent manner. Maximal effects of 23.2% (5% rivastigmine), 19.6% (2 % rivastigmine) and 15.2% (1% rivastigmine) were achieved 1, 3 and 5 hr aft er application of the drug. A non-significant reduction of IOP in the contr alateral eye was also observed. Rabbits evidenced no signs of discomfort af ter administration of rivastigmine. No conjunctival discharge or other sign s of drug related local toxicity were found. Rivastigmine, a selective antagonist of AChE, lowers IOP significantly and may thus be of potential use in glaucoma therapy.