Aceclidine hydrochloride

Aceclidine hydrochloride (3-acetoxyquinuclidine, "Glaucostat": Chibret) used topically in a strength of 2 per cent. is a parasympathomimetic drug acting directly on the motor end-plate (cholinergic nerve-endings). It is suitable for administration as eye drops, penetrating rapidly into the anterior chamber. It is a synthetic substance and was first prepared in Russia by Rubitzov and Miklina (i 960). The name "Aceclidine" was coined by Mashkovski and Zaitzeva (i960), who studied its pharmacological aspects. It was also described by Sharts and Shulpina (I96I). Numerous clinical trials in Russia, France, and Italy and in other countries have led to its widespread use on the continent of Europe, including the U.S.S.R. In several centres it is used routinely as an alternative to pilocarpine or when pilocarpine fails. The drug has also been investigated in the United States of America by Lieberman and Leopold (i967), who described a definite lowering of intraocular pressure with no corresponding increase in facility of outflow. Aceclidine is not in clinical use in the U.S.A. Our interest was stimulated by these early reports. No fully satisfactory topical directacting parasympathomimetic drug is available as an alternative to pilocarpine if for any reason this is or becomes unsuitable. In such cases resort is usually made to cholinesteraseinhibiting substances eserine, prostigmine (neostigmine), or one of the "irreversible" cholinesterase inhibitors, di-isopropylfluorophosphonate (DFP), phospholine iodide, demecarium bromide, etc. The use of the latter group of drugs is not without its disadvantages or dangers. Of the available direct parasympathetic stimulating drops, acetylcholine itself is too unstable to remain in solution for more than a few minutes. Carcholin (carbachol, Doryl, carbamylcholine chloride, a synthetic drug) o075 to 3 per cent. has poor corneal penetration, being hydrophilic, and must be used with a wetting agent in methyl cellulose (Shaffer, I967), or as a dry suspension in anhydrous vehicles (Swan, 1959). Methacholine (Mlecholyl) I0 to 20 per cent. is unstable and short-acting and must be used every 5 to o0 minutes. Arecoline, the alkaloid of the betel nut, was tried in ophthalmology in i895 but never used in practice. Its formula is similar to that of aceclidine. Furmethide (furfuryl methyl ammonium iodide) and urecholine (urethane of beta-methyl choline) have also been abandoned. Among the obvious advantages that aceclidine appears to offer over the preceding drugs are its stability, penetration, and long shelf-life.