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Identification
NameDemecarium
Accession NumberDB00944  (APRD00905)
Typesmall molecule
Groupsapproved
Description

Demecarium is an indirect-acting parasympathomimetic agent that is used to treat glaucoma. It is a cholinesterase inhibitor or an anticholinesterase. Cholinesterase inhibitors prolong the effect of acetylcholine, which is released at the neuroeffector junction of parasympathetic postganglion nerves, by inactivating the cholinesterases that break it down. Demecarium inactivates both pseudocholinesterase and acetylcholinesterase. In the eye, this causes constriction of the iris sphincter muscle (causing miosis) and the ciliary muscle. The outflow of the aqueous humor is facilitated, which leads to a reduction in intraocular pressure.

Structure
Thumb
Synonyms
SynonymLanguageCode
DemecariumNot AvailableNot Available
Salts
Name/CAS Structure Properties
Demecarium bromide
56-94-0
Thumb
  • InChI Key: YHKBUDZECQDYBR-UHFFFAOYSA-L
  • Monoisotopic Mass: 714.235531466
  • Average Mass: 716.588
DBSALT000567
Brand names
NameCompany
HumorsolMSD
TonilenNot Available
TosmilenNot Available
Brand mixturesNot Available
Categories
CAS numberNot Available
WeightAverage: 556.7797
Monoisotopic: 556.398856172
Chemical FormulaC32H52N4O4
InChI KeyRWZVPVOZTJJMNU-UHFFFAOYSA-N
InChI
InChI=1S/C32H52N4O4/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/q+2
IUPAC Name
N,N,N-trimethyl-3-{[methyl(10-{methyl[3-(trimethylazaniumyl)phenoxycarbonyl]amino}decyl)carbamoyl]oxy}anilinium
SMILES
CN(CCCCCCCCCCN(C)C(=O)OC1=CC=CC(=C1)[N+](C)(C)C)C(=O)OC1=CC=CC(=C1)[N+](C)(C)C
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassPhenol Ethers
Direct parentPhenol Ethers
Alternative parentsDicarboxylic Acids and Derivatives; Tertiary Amines; Carbamic Acids and Derivatives; Polyamines; Ethers
Substituentsdicarboxylic acid derivative; tertiary amine; carbamic acid derivative; polyamine; ether; amine; organonitrogen compound
Classification descriptionThis compound belongs to the phenol ethers. These are aromatic compounds containing an ether group substituted with a benzene ring.
Pharmacology
IndicationFor the topical treatment of chronic open-angle glaucoma.
PharmacodynamicsDemecarium is a long-acting cholinesterase inhibitor and potent miotic. Because of its toxicity, it should be reserved for use in patients with open-angle glaucoma or other chronic glaucomas not satisfactorily controlled with the short-acting miotics and other agents. Application of demecarium to the eye produces intense miosis and ciliary muscle contraction due to inhibition of cholinesterase, allowing acetylcholine to accumulate at sites of cholinergic transmission. These effects are accompanied by increased capillary permeability of the ciliary body and iris, increased permeability of the blood-aqueous barrier, and vasodilation. Myopia may be induced or, if present, may be augmented by the increased refractive power of the lens that results from the accommodative effect of the drug.
Mechanism of actionDemecarium is an indirect-acting parasympathomimetic agent, also known as a cholinesterase inhibitor and anticholinesterase. Cholinesterase inhibitors prolong the effect of acetylcholine, which is released at the neuroeffector junction of parasympathetic postganglion nerves, by inactivating the cholinesterases that break it down. Demecarium inactivates both pseudocholinesterase and acetylcholinesterase. 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). The outflow of the aqueous humor is facilitated, which leads to a reduction in intraocular pressure. Of the two actions, the effect on the accommodation reflex is the more transient and generally disappears before termination of the miosis.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityThe oral LD50 is 2.96 mg/kg in the mouse. Symptoms of overdose include nausea, vomiting, abdominal cramps, diarrhea, urinary incontinence, salivation, sweating, difficulty in breathing, bradycardia, or cardiac irregularities.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption - 0.975
Blood Brain Barrier + 0.8552
Caco-2 permeable + 0.5237
P-glycoprotein substrate Substrate 0.6145
P-glycoprotein inhibitor I Non-inhibitor 0.778
P-glycoprotein inhibitor II Inhibitor 0.6802
Renal organic cation transporter Non-inhibitor 0.6822
CYP450 2C9 substrate Non-substrate 0.7289
CYP450 2D6 substrate Non-substrate 0.7984
CYP450 3A4 substrate Substrate 0.707
CYP450 1A2 substrate Non-inhibitor 0.8801
CYP450 2C9 substrate Non-inhibitor 0.8903
CYP450 2D6 substrate Non-inhibitor 0.9166
CYP450 2C19 substrate Non-inhibitor 0.8855
CYP450 3A4 substrate Non-inhibitor 0.88
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8541
Ames test Non AMES toxic 0.6225
Carcinogenicity Non-carcinogens 0.684
Biodegradation Not ready biodegradable 0.9618
Rat acute toxicity 2.5848 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.7692
hERG inhibition (predictor II) Inhibitor 0.5084
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
SolutionOphthalmic
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point164-170Schrnid, O.; US. Patent 2,789,981; April 23, 1957; assigned to Oesterreichische Stickstoffwerke AG, Austria.
logP-1.75Not Available
Predicted Properties
PropertyValueSource
water solubility1.69e-05 g/lALOGPS
logP0.65ALOGPS
logP-1.4ChemAxon
logS-7.6ALOGPS
physiological charge2ChemAxon
hydrogen acceptor count2ChemAxon
hydrogen donor count0ChemAxon
polar surface area59.08ChemAxon
rotatable bond count17ChemAxon
refractivity185.71ChemAxon
polarizability64.49ChemAxon
number of rings2ChemAxon
bioavailability0ChemAxon
rule of fiveNoChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Schrnid, O.; US. Patent 2,789,981; April 23, 1957; assigned to Oesterreichische Stickstoffwerke AG, Austria.

General Reference
  1. Ward DA, Abney K, Oliver JW: The effects of topical ocular application of 0.25% demecarium bromide on serum acetylcholinesterase levels in normal dogs. Vet Ophthalmol. 2003 Mar;6(1):23-5. Pubmed
  2. Krohne SG: Effect of topically applied 2% pilocarpine and 0.25% demecarium bromide on blood-aqueous barrier permeability in dogs. Am J Vet Res. 1994 Dec;55(12):1729-33. Pubmed
  3. Gum GG, Gelatt KN, Gelatt JK, Jones R: 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. Pubmed
External Links
ResourceLink
KEGG DrugD00667
PubChem Compound5965
PubChem Substance46507824
Therapeutic Targets DatabaseDAP000894
PharmGKBPA164745610
RxListhttp://www.rxlist.com/cgi/generic2/demecarium.htm
Drugs.comhttp://www.drugs.com/mtm/demecarium-bromide-ophthalmic.html
WikipediaDemecarium_bromide
ATC CodesS01EB04
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
TacrineThe acetylcholinesterase inhibitor, Tacrine, may increase the adverse/toxic effects of Demcarium, a cholinergic agonist. Monitor for increased cholinergic effects and toxicity.
Food InteractionsNot Available

Targets

1. Acetylcholinesterase

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Acetylcholinesterase P22303 Details

References:

  1. Ward DA, Abney K, Oliver JW: The effects of topical ocular application of 0.25% demecarium bromide on serum acetylcholinesterase levels in normal dogs. Vet Ophthalmol. 2003 Mar;6(1):23-5. Pubmed
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Cholinesterase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cholinesterase P06276 Details

References:

  1. Meiniel R: Neuromuscular blocking agents and axial teratogenesis in the avian embryo. Can axial morphogenetic disorders by explained by pharmacological action upon muscle tissue? Teratology. 1981 Apr;23(2):259-71. Pubmed
  2. Gum GG, Gelatt KN, Gelatt JK, Jones R: 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. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on April 10, 2014 13:37