Aceclidine

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Aceclidine
Aceclidine.svg
Aceclidine 3D ball.png
Clinical data
Other namesLNZ101
AHFS/Drugs.com Vizz
License data
Routes of
administration 		Topical (ophthalmic solution)
ATC code
Legal status
Legal status
Identifiers
  • 1-Azabicyclo[2.2.2]oct-3-yl acetate; 3-Quinuclidinyl Acetate
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.011.431 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C9H15NO2
Molar mass 169.224 g·mol−1
3D model (JSmol)
  • O=C(OC2C1CCN(CC1)C2)C
  • InChI=1S/C9H15NO2/c1-7(11)12-9-6-10-4-2-8(9)3-5-10/h8-9H,2-6H2,1H3
  • Key:WRJPSSPFHGNBMG-UHFFFAOYSA-N

Aceclidine is a parasympathomimetic cholinergic drug that functions as a muscarinic acetylcholine receptor agonist. [2] It is used in ophthalmology as a miotic agent to constrict the pupil. Historically used in Europe for the treatment of glaucoma, aceclidine received its first U.S. approval in 2025 under the brand name Vizz as a topical eye drop for the correction of presbyopia. [3] Its mechanism of action produces pupil contraction with a relatively minimal effect on the ciliary muscle, which improves near visual acuity through a " pinhole " depth-of-field effect without inducing significant accommodative spasm.

Contents

Medical uses

Glaucoma

As a parasympathomimetic miotic, aceclidine decreases intraocular pressure by stimulating muscarinic receptors in the eye, which constricts the pupil and opens the trabecular meshwork to facilitate aqueous 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 as pilocarpine, 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 as beta-blockers and prostaglandin analogs, became available. [6] [7]

Presbyopia

In 2025, the U.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 the depth of focus and improves near vision. Data from the Clarity 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 a pilocarpine-based product approved in 2021. [11] [12]

Pharmacology

Pharmacokinetics

Aceclidine, when administered ophthalmically, is absorbed primarily through the conjunctival and corneal 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 significant systemic 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]

Mechanism of action

Aceclidine is a selective muscarinic acetylcholine receptor agonist used primarily as an ophthalmic agent. Its mechanism of action involves binding preferentially to muscarinic receptors on the iris sphincter muscle, leading to pupillary constriction (miosis) with minimal stimulation of the ciliary muscle. Unlike non-selective miotic agents such as pilocarpine, aceclidine’s selectivity results in a pronounced reduction in pupil size without significant induction of accommodation or myopic shift, thereby minimizing side effects like lens thickening or accommodative spasm. This targeted action is leveraged in the treatment of presbyopia, where the drug induces a “pinhole” effect: by creating a small, stable pupil, aceclidine increases the depth 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]

Chemistry

Aceclidine is an organic compound that is structurally related to quinuclidine. As such its alternative name is 3-acetoxyquinuclidine. Its protonated derivative has a pKa of 9.3. [16]

History

Aceclidine (3-acetoxyquinuclidine) was first synthesized by researchers in the Soviet 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 the United States at that time, it was used clinically in other countries as a topical agent to lower intraocular pressure. [19] By the 1970s, it was available under various brand names, including Glaucostat, Glaucotat, Glaunorm, and Glaudin. [19] A combination product with epinephrine was also marketed as Glaucadrine. [20] These formulations were used to manage glaucoma, particularly in cases where miosis facilitates a reduction in intraocular pressure. [19]

Research

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 on accommodation. [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 were Phase 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]

References

  1. ↑ LENZ Therapeutics, Inc. "VIZZ (aceclidine ophthalmic solution) 1.44%, for topical ophthalmic use" (PDF). Highlights of Prescribing Information. U.S. Food and Drug Administration.
  2. ↑ Shannon HE, Hart JC, Bymaster FP, Calligaro DO, DeLapp NW, Mitch CH, et al. (August 1999). "Muscarinic receptor agonists, like dopamine receptor antagonist antipsychotics, inhibit conditioned avoidance response in rats". The Journal of Pharmacology and Experimental Therapeutics. 290 (2): 901–907. doi:10.1016/S0022-3565(24)34979-1. PMID   10411607.
  3. ↑ Paul A (7 August 2025). "Bye bye, bifocals? New eye drops can fix farsightedness". Popular Science.
  4. ↑ 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. PMID   6036300.
  5. ↑ 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. PMID   1110190.
  6. ↑ Maul EA, Maul EJ (2016). "Medical Treatment: First-Line Agents, Monotherapy, and Combination Therapy". Pearls of Glaucoma Management. pp. 227–242. doi:10.1007/978-3-662-49042-6_24. ISBN   978-3-662-49040-2.
  7. ↑ Sambhara D, Aref AA (January 2014). "Glaucoma management: relative value and place in therapy of available drug treatments". Therapeutic Advances in Chronic Disease. 5 (1): 30–43. doi:10.1177/2040622313511286. PMC   3871276 . PMID   24381726.
  8. 1 2 Clinical trial number NCT05656027 for "A Multi-Center, Double-Masked Phase 3 Evaluation of the Safety and Efficacy of LNZ101 for the Treatment of Presbyopia" at ClinicalTrials.gov
  9. 1 2 Clinical trial number NCT05728944 for "A Multi-Center, Double-Masked Phase 3 Evaluation of the Safety and Efficacy of LNZ101 for the Treatment of Presbyopia" at ClinicalTrials.gov
  10. 1 2 Puckey M (ed.). "Vizz (aceclidine): Uses, Dosage, Side Effects, Warnings". Drugs.com.
  11. 1 2 3 Mullard A (August 2025). "FDA grants first US approval for decades-old eye drug". Nature Reviews. Drug Discovery. doi:10.1038/d41573-025-00138-3. PMID   40775091.
  12. ↑ Butterfield M (8 August 2025). "No more reading glasses? New FDA-approved eye drops can fix your near vision - National". Global News.
  13. 1 2 Grzybowski A, Markeviciute A, Zemaitiene R (2020). "A Review of Pharmacological Presbyopia Treatment". Asia-Pacific Journal of Ophthalmology. 9 (3). Philadelphia, Pa.: 226–233. doi:10.1097/APO.0000000000000297. PMC   7299227 . PMID   32511122.
  14. ↑ Agrahari V, Mandal A, Agrahari V, Trinh HM, Joseph M, Ray A, et al. (December 2016). "A comprehensive insight on ocular pharmacokinetics". Drug Delivery and Translational Research. 6 (6): 735–754. doi:10.1007/s13346-016-0339-2. PMC   5319401 . PMID   27798766.
  15. ↑ Grzybowski A, Kapitanovaite L, Zemaitiene R (2024). "An updated systematic review of pharmacological treatments for presbyopia". Advances in Ophthalmology Practice and Research. 4 (4): 220–225. doi:10.1016/j.aopr.2024.09.001. PMC   11541684 . PMID   39512930.
  16. ↑ 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. PMID   12558387.
  17. 1 2 3 Romano JH (August 1970). "Double-blind cross-over comparison of aceclidine and pilocarpine in open-angle glaucoma". The British Journal of Ophthalmology. 54 (8): 510–521. doi:10.1136/bjo.54.8.510. PMC   1207904 . PMID   4917903.
  18. ↑ 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. PMID   13767763.
  19. 1 2 3 "Aceclidine Hydrochloride". Inxight Drugs. NCATS.
  20. ↑ "Aceclidine". MeSH Browser. U.S. National Library of Medicine.
  21. ↑ 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. PMID   5314009.
  22. ↑ 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. PMID   6125875.
  23. ↑ Clinical trial number NCT05753189 for "Phase 3 Safety Study for the Treatment of Presbyopia Subjects" at ClinicalTrials.gov
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