Aceclidine hydrochloride
[CAS# 6109-70-2]

Identification

• Classification: Organic raw materials >> Carboxylic compounds and derivatives >> Salt of carboxylic acid ester and its derivatives
• Name: Aceclidine hydrochloride
• Synonyms: 1-azabicyclo[2.2.2]octan-3-yl acetate;hydrochloride
• Molecular Formula: C₉H₁₆ClNO₂
• Molecular Weight: 205.68
• CAS Registry Number: 6109-70-2
• EC Number: 228-071-5
• SMILES: CC(=O)OC1CN2CCC1CC2.Cl

Safety Data

• Hazard Symbols: GHS06 Danger
• Hazard Statements: H301-H311
• Precautionary Statements: P262-P264-P270-P280-P301+P316-P302+P352-P316-P321-P330-P361+P364-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	3	H301
Acute toxicity	Acute Tox.	3	H311

• Transport Information: UN 2811

Discovory and Applicatios

Aceclidine hydrochloride is a quinuclidine derivative and a cholinergic agonist used primarily in ophthalmology. Chemically, it is a bicyclic amine in which the quinuclidine ring is substituted at the 3-position with a carboxylic acid ester that is protonated as a hydrochloride salt. The compound acts as a muscarinic acetylcholine receptor agonist, with particular selectivity toward the M3 receptor subtype, which mediates smooth muscle contraction and exocrine gland secretion. This property underpins its primary therapeutic application in the treatment of glaucoma.

The discovery of aceclidine traces back to research into quinuclidine analogues of acetylcholine during the mid-20th century, when medicinal chemists were exploring muscarinic receptor agonists for ocular use. The quinuclidine framework was identified as providing both chemical stability and a rigid bicyclic structure that allows selective receptor interaction. The hydrochloride form enhances water solubility, facilitates formulation, and ensures chemical stability for pharmaceutical use.

Pharmacologically, aceclidine hydrochloride functions by binding to muscarinic receptors in the ciliary muscle of the eye. Activation of M3 receptors in this tissue leads to contraction of the ciliary muscle, which in turn increases aqueous humor outflow through the trabecular meshwork. This results in a reduction of intraocular pressure, making aceclidine useful in patients with open-angle glaucoma. The compound has a relatively rapid onset of action when administered topically and exhibits a duration suitable for therapeutic dosing schedules.

Aceclidine hydrochloride also demonstrates effects on other muscarinic sites, including the salivary and lacrimal glands, due to the widespread distribution of M3 receptors. Systemic absorption can lead to cholinergic side effects, including sweating, salivation, and gastrointestinal stimulation, although these are minimized by local ocular administration. The pharmacokinetic profile of aceclidine is influenced by its polar hydrochloride salt form, which limits systemic distribution and facilitates rapid clearance from the bloodstream after ocular absorption.

Chemically, aceclidine hydrochloride is prepared through synthetic routes that begin with quinuclidine, a bicyclic secondary amine. Functionalization at the 3-position introduces the acetyl ester or related substituent, followed by formation of the hydrochloride salt. The compound is stable under standard storage conditions, although like many amines, it is sensitive to strong oxidizing agents and extreme pH conditions. Proper storage in sealed containers at controlled temperatures is recommended to maintain potency and purity.

In addition to its ophthalmic application, aceclidine hydrochloride has been used as a pharmacological tool in experimental settings to study muscarinic receptor physiology. Its selectivity for M3 receptors allows researchers to investigate receptor-mediated smooth muscle contraction and exocrine gland function. Animal studies have utilized aceclidine to probe the effects of selective muscarinic stimulation in gastrointestinal and cardiovascular tissues, providing insight into receptor pharmacodynamics.

Overall, aceclidine hydrochloride represents a chemically and pharmacologically well-characterized muscarinic agonist. Its rigid quinuclidine structure, selective M3 receptor activity, and formulation as a hydrochloride salt make it effective for ocular use, particularly in lowering intraocular pressure in glaucoma patients. Beyond clinical application, its role as a research tool in muscarinic pharmacology underscores the importance of selective receptor agonists in understanding physiological processes and in the development of therapeutics targeting the cholinergic system.

References

2023. A multilevel screening pipeline in zebrafish identifies therapeutic drugs for GAN. EMBO Molecular Medicine, 15(7).
DOI: 10.15252/emmm.202216267

2023. Pharmacological Treatments for Presbyopia. Drugs & Aging, 40(2).
DOI: 10.1007/s40266-022-01002-4