In normotensive beagle dogs with hereditary glaucoma, mecarium bromide (0.125 and 0.5%) lowers intraocular pressure (IOP) and produces long-term miosis [1].

Absorption, Distribution and Excretion
Demethasone can be absorbed through the conjunctival sac and intact skin…/Demethasone/

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/

[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.

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.)