Demecarium bromide acts by inhibiting the enzyme acetylcholinesterase, leading to increased levels of acetylcholine at neuromuscular junctions and synapses. It inactivates both pseudocholinesterase and acetylcholinesterase, thereby preventing the breakdown of acetylcholine and increasing its activity. In the eye, this causes constriction of the iris sphincter muscle (causing miosis) and the ciliary muscle, affecting the accommodation reflex and causing a spasm of the focus to near vision.

In vitro, demecarium bromide acts as an acetylcholinesterase inhibitor. By inhibiting both pseudocholinesterase and acetylcholinesterase, it leads to an accumulation of acetylcholine at sites of cholinergic transmission. This activity is the basis for its parasympathomimetic effects and its use in diagnostic applications.

In normotensive beagle dogs with hereditary glaucoma, mecarium bromide (0.125 and 0.5%) lowers intraocular pressure (IOP) and produces long-term miosis [1].
In vivo, demecarium bromide is used in the treatment of chronic open-angle glaucoma. When used topically, it inactivates both pseudocholinesterase and acetylcholinesterase in the eye, thereby preventing acetylcholine breakdown and increasing acetylcholine activity. This causes constriction of the iris sphincter muscle and the ciliary muscle, facilitating the outflow of the aqueous humor and so reducing intraocular pressure. It is one of several topical medications used to reduce elevated intraocular pressure (IOP) associated with primary glaucoma in cats, dogs, and other animals.

In vitro enzyme assays for demecarium bromide typically measure its ability to inhibit acetylcholinesterase and pseudocholinesterase activity. The enzyme is incubated with its substrate (acetylthiocholine) in the presence of increasing concentrations of the compound. Enzyme activity is measured spectrophotometrically using Ellman's reagent. IC50 values are calculated from dose-response curves to quantify the compound's potency.

Cell-based assays for demecarium bromide are not commonly used due to its mechanism of action as an enzyme inhibitor. However, its effects on cholinergic signaling can be studied in cells expressing acetylcholinesterase. The compound's ability to inhibit enzyme activity and increase acetylcholine levels can be assessed by measuring acetylcholine accumulation in the culture medium.

In vivo animal studies for demecarium bromide are primarily conducted in the context of glaucoma research. Animal models, such as rabbits or dogs, are used to evaluate the compound's ability to reduce intraocular pressure. The compound is administered topically, and its effects on pupil size, accommodation, and intraocular pressure are measured.

Absorption, Distribution and Excretion
Demethasone can be absorbed through the conjunctival sac and intact skin…/Demethasone/
Demecarium bromide is a quaternary ammonium compound and, as such, is poorly absorbed systemically. When applied topically to the eye, it exerts its effects locally. The compound's long duration of action allows for less frequent dosing compared to other cholinesterase inhibitors. Its metabolism and systemic elimination are not well-characterized.

Interactions
The inhibitory effect of demecalin is reversible. Atropine and pralidoxime (protopanol) can antagonize the local effects of this drug. Pre-infusion of physostigmine does not inhibit the effects of demecalin. /Demecalin/
Demecarium bromide is a potent cholinesterase inhibitor and, as such, can cause significant toxicity if systemically absorbed. Adverse effects may include bradycardia, hypotension, and gastrointestinal disturbances. Due to its toxicity, its use is limited to topical application in the eye. It is contraindicated in patients with known hypersensitivity to cholinesterase inhibitors.

[1]. Activation and blockade of cardiac muscarinic receptors by endogenous acetylcholine and cholinesterase inhibitors. J Pharmacol Exp Ther. 1982 Oct;223(1):20-4.

[2]. Effect of topically applied demecarium bromide and echothiophate iodide on intraocular pressure and pupil size in beagles with normotensive eyes and beagles with inherited glaucoma. Am J Vet Res. 1993 Feb;54(2):287-93.

Demecarium bromide is the methyl bromide salt of the N,N'-bis[3-(dimethylamino)phenylcarbamate] derivative of 2,13-diazatetradecane. It is a long-acting inhibitor of acetylcholinesterase and pseudocholinesterase. It is used to treat chronic open-angle glaucoma: intraocularly, it causes contraction of the iris sphincter and ciliary muscle, promoting aqueous humor outflow and thus lowering intraocular pressure. It is an EC 3.1.1.8 (cholinesterase) inhibitor and an EC 3.1.1.7 (acetylcholinesterase) inhibitor. It is a quaternary ammonium salt, bromide salt, and carbamate. It contains Demecarium. Demecarium bromide is the bromide salt form of Demecarium, a quaternary ammonium compound and a long-acting cholinesterase inhibitor with parasympathomimetic activity. When used topically, demecalin inactivates pseudocholinesterase and acetylcholinesterase, thereby preventing the breakdown of acetylcholine and increasing its activity. This leads to contraction of the iris sphincter (resulting in pupillary constriction) and ciliary muscle (affecting the accommodation reflex). In this way, the drug increases aqueous humor outflow, thereby lowering intraocular pressure.
See also: Demecalammonium (containing the active ingredient).

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Mechanism of Action
/Increases aqueous humor outflow/...accompanied by conjunctival vasodilation and increased blood-aqueous humor barrier permeability. Simultaneously, the indirect activity of the converging muscle is also reduced. ...The cholinesterase inhibition induced by demecalammonium is "reversible".
Demecalammonium bromide...is a quaternary ammonium salt anticholinesterase drug. The accumulation of acetylcholine leads to pupillary constriction and stimulates the ciliary muscle...lowering intraocular pressure by increasing aqueous humor outflow.

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Therapeutic Uses
Cholinesterase Inhibitor; Miotic
/Treatment of Esotropia/ If it is still necessary to instill drops every two days, treatment should be discontinued after 4 months.
/Congestive Iritis, Iridocyclitis, Conjunctival Congestion and Intraocular Congestion/…can be relieved by instilling the lowest effective concentration of solution before bedtime and usually subsides within the first few days of treatment. If pericardial congestion is severe, instilling a 10% phenylephrine hydrochloride solution may be helpful.
After instilling demecalin, pupillary constriction will occur within 1 hour and reach its maximum within 2 to 4 hours. Intraocular pressure decreases approximately after 12 hours, usually preceded by a slight increase in intraocular pressure. After a single instillation, pupillary constriction and the decrease in intraocular pressure may last for a week or longer.
For more complete data on the therapeutic uses of demecalamine bromide (10 types), please visit the HSDB record page.

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Drug Warnings
Gonioscopy should be performed before demecaine treatment to confirm glaucoma opening…Intraocular pressure may increase and acute attacks may occur in patients with narrow-angle (congestive) glaucoma.Even with glaucoma opening, intraocular pressure may still increase.
Demecaine is contraindicated in patients with markedly unstable vasomotor function, bronchial asthma, spastic gastrointestinal disorders, peptic ulcers, severe bradycardia or hypotension, recent myocardial infarction, epilepsy, or Parkinson's disease.
Demecaine should be used with caution, or even contraindicated, in patients with a history of retinal detachment and elevated intraocular pressure accompanied by intraocular inflammation. ...Contraindicated in patients with narrow-angle glaucoma.
/Dexamethasone/...should not be used before iridectomy for angle-closure glaucoma because...it is more likely to worsen angle closure than weak miotics.
Demecarium bromide is a long-acting cholinesterase inhibitor used primarily for the treatment of chronic open-angle glaucoma. It is a quaternary ammonium compound and a potent miotic. Its use has declined with the availability of other glaucoma medications. It remains a valuable research tool for studying cholinergic transmission and cholinesterase inhibition.

C32H52N4O4.2BR

716.59

714.235

56-94-0

16505-84-3 (cation);56-94-0 (bromide);

5965

White to off-white solid powder

164 - 170ºC

0.77

0

6

17

42

686

0

YHKBUDZECQDYBR-UHFFFAOYSA-L

InChI=1S/C32H52N4O4.2BrH/c1-33(31(37)39-29-21-17-19-27(25-29)35(3,4)5)23-15-13-11-9-10-12-14-16-24-34(2)32(38)40-30-22-18-20-28(26-30)36(6,7)8;;/h17-22,25-26H,9-16,23-24H2,1-8H3;2*1H/q+2;;/p-2

trimethyl-[3-[methyl-[10-[methyl-[3-(trimethylazaniumyl)phenoxy]carbonylamino]decyl]carbamoyl]oxyphenyl]azanium;dibromide

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~160 mg/mL (~223.28 mM)

Solubility in Formulation 1: ≥ 2.67 mg/mL (3.73 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 26.7 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.67 mg/mL (3.73 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 26.7 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.67 mg/mL (3.73 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 26.7 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)