As a parasympathomimetic miotic, aceclidine decreases intraocular pressure by stimulating muscarinic receptors in the eye, which constricts the pupil and opens thetrabecular meshwork to facilitateaqueous humor outflow. It was used as a topical drop in the treatment of narrow-angle and open-angle glaucoma.[4] The clinical utility of aceclidine in glaucoma is comparable to other cholinergic miotics such aspilocarpine, though aceclidine was associated with less ciliary muscle spasm and fewer accommodative disturbances.[5] The use of aceclidine for chronic glaucoma management has declined as other therapeutic classes, such asbeta-blockers andprostaglandin analogs, became available.[6][7]
In 2025, theU.S. Food and Drug Administration (FDA) approved aceclidine 1.44 % ophthalmic solution (Vizz) for the topical treatment of presbyopia. The treatment involves a once-daily application to constrict the pupil, creating a pinhole effect that increases thedepth of focus and improves near vision. Data from theClarity 1 and 2 clinical trials showed that the administration of aceclidine resulted in a statistically significant improvement in near visual acuity within approximately 30 minutes, with a duration of effect of up to 8–10 hours.[8][9] Distance vision was not significantly affected due to the drug's limited action on the ciliary muscle. No serious adverse events were reported in the trials. Common side effects included transient ocular irritation, mild headache, and reduced vision in low-light conditions.[10] Aceclidine became the second pharmacological agent approved for presbyopia in the U.S., following apilocarpine-based product approved in 2021.[11][12]
Aceclidine, when administered ophthalmically, is absorbed primarily through theconjunctival andcorneal tissues. Its onset of action is rapid due to efficient local absorption. Systemically, aceclidine undergoes limited metabolism, as its primary site of effect is the eye, thereby minimizing significantsystemic exposure. Distribution following ocular administration is predominantly localized, with low risk of systemic accumulation. Excretion details are not extensively characterized, but, like other topical miotic agents, aceclidine is presumed to have minimal systemic bioavailability and is likely eliminated primarily via the local ocular route and normal metabolic pathways.[13][14][10]
Aceclidine is a selectivemuscarinic acetylcholine receptor agonist used primarily as an ophthalmic agent. Its mechanism of action involves binding preferentially tomuscarinic receptors on theiris sphincter muscle, leading to pupillary constriction (miosis) with minimal stimulation of theciliary muscle. Unlike non-selective miotic agents such aspilocarpine, aceclidine's selectivity results in a pronounced reduction in pupil size without significant induction of accommodation ormyopic shift, thereby minimizing side effects like lens thickening oraccommodative spasm. This targeted action is leveraged in the treatment ofpresbyopia, where the drug induces a “pinhole” effect: by creating a small, stable pupil, aceclidine increases thedepth of focus and improves near vision while maintaining distance visual acuity. Its limited activity on the ciliary muscle distinguishes it from other cholinergic agonists and offers a favorable safety profile, with a reduced risk of retina or vitreous traction and fewer accommodative disturbances.[13][15]
Aceclidine is anorganic compound that is structurally related toquinuclidine. As such its alternative name is 3-acetoxyquinuclidine. Its protonated derivative has apKa of 9.3.[16]
Aceclidine (3-acetoxyquinuclidine) was first synthesized by researchers in theSoviet Union in the early 1960s, and its mitotic properties were subsequently investigated for glaucoma therapy.[17][18] It was introduced in European ophthalmology by the late 1960s. In several European countries, it was marketed by Chibret under the trade name Glaucostat.[17] Although not approved in theUnited States at that time, it was used clinically in other countries as a topical agent to lowerintraocular pressure.[19] By the 1970s, it was available under various brand names, including Glaucostat, Glaucotat, Glaunorm, and Glaudin.[19] A combination product withepinephrine was also marketed as Glaucadrine.[20] These formulations were used to manage glaucoma, particularly in cases wheremiosis facilitates a reduction in intraocular pressure.[19]
Aceclidine has been a subject of clinical and pharmacological research since the 1960s.[17] Early studies in the 1970s compared its efficacy for glaucoma to that of pilocarpine, finding it produced a similar reduction in intraocular pressure with a lesser effect onaccommodation.[21] Research in the 1980s on its optical isomers determined the (+)-enantiomer was the primary source of its cholinergic activity.[22]
In the 2010s, research refocused on aceclidine as a potential treatment for presbyopia due to its pupil-selective mechanism. Under the development code PRX-100, Lenz Therapeutics conducted the Clarity 1, 2, and 3 clinical trials.[11] Clarity 1 and 2 werePhase III trials that evaluated aceclidine 1.44 % in adults with presbyopia and met all primary and secondary endpoints for improving near visual acuity.[8][9] Clarity 3 was a long-term study that confirmed the drug's safety and tolerability over a six-month period.[23] The results of these trials formed the basis for its FDA approval in 2025.[11]
^Lieberman TW, Leopold IH (September 1967). "The use of aceclydine in the treatment of glaucoma. Its effect on intraocular pressure and facility of aqueous humor outflow as compared to that of pilocarpine".American Journal of Ophthalmology.64 (3):405–415.doi:10.1016/0002-9394(67)92004-1.PMID6036300.
^Fechner PU, Teichmann KD, Weyrauch W (January 1975). "Accommodative effects of aceclidine in the treatment of glaucoma".American Journal of Ophthalmology.79 (1):104–106.doi:10.1016/0002-9394(75)90464-X.PMID1110190.
^abClinical trial numberNCT05656027 for "A Multi-Center, Double-Masked Phase 3 Evaluation of the Safety and Efficacy of LNZ101 for the Treatment of Presbyopia" atClinicalTrials.gov
^abClinical trial numberNCT05728944 for "A Multi-Center, Double-Masked Phase 3 Evaluation of the Safety and Efficacy of LNZ101 for the Treatment of Presbyopia" atClinicalTrials.gov
^Aggarwal VK, Emme I, Fulford SY (February 2003). "Correlation between pK(a) and reactivity of quinuclidine-based catalysts in the Baylis-Hillman reaction: discovery of quinuclidine as optimum catalyst leading to substantial enhancement of scope".The Journal of Organic Chemistry.68 (3):692–700.doi:10.1021/jo026671s.PMID12558387.
^Mashkovskii MD, Zaitseva KA (1960). "[On the pharmacology of 3-acetoxyquinuclidine (aceclidine)]" [On the pharmacology of 3-acetoxyquinuclidine (aceclidine)].Farmakologiia I Toksikologiia [Pharmacology and toxicology] (in Russian).23:398–406.PMID13767763.
^"Aceclidine".MeSH Browser. U.S. National Library of Medicine.
^Meythaler H, Ruppert W (April 1971). "[The myopic and miotic effect of pilocarpin and glaucostat]".Albrecht von Graefes Archiv für Klinische und Experimentelle Ophthalmologie.181 (3):234–245.doi:10.1007/BF02390254.PMID5314009.
^Ringdahl B, Ehler FJ, Jenden DJ (May 1982). "Muscarinic activity and receptor binding of the enantiomers of aceclidine and its methiodide".Molecular Pharmacology.21 (3):594–599.doi:10.1016/S0026-895X(25)14912-2.PMID6125875.
^Clinical trial numberNCT05753189 for "Phase 3 Safety Study for the Treatment of Presbyopia Subjects" atClinicalTrials.gov
Clinical trial number(NCT05656027 for "Phase 3 Evaluation of the Safety and Efficacy of LNZ101 for the Treatment of Presbyopia (CLARITY)" atClinicalTrials.gov
Clinical trial number(NCT05728944 for "Phase 3 Efficacy Study of LNZ101 for the Treatment of Presbyopia (CLARITY)" atClinicalTrials.gov
Clinical trial number(NCT05753189 for "Phase 3 Safety Study for the Treatment of Presbyopia Subjects" atClinicalTrials.gov
