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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
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International Brands
NameCompany
HumorsolMSD
TonilenNot Available
TosmilenNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Demecarium bromide
56-94-0
Thumb
  • InChI Key: YHKBUDZECQDYBR-UHFFFAOYSA-L
  • Monoisotopic Mass: 714.235531466
  • Average Mass: 716.588
DBSALT000567
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
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as substituted anilines. These are organic compound containing an aniline group substituted at one or more positions.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassAnilines
Direct ParentSubstituted anilines
Alternative Parents
Substituents
  • Substituted aniline
  • Dicarboxylic acid or derivatives
  • Tertiary amine
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Organic cation
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
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
MetabolismNot Available
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
PropertyValueProbability
Human Intestinal Absorption-0.975
Blood Brain Barrier+0.8552
Caco-2 permeable+0.5237
P-glycoprotein substrateSubstrate0.6145
P-glycoprotein inhibitor INon-inhibitor0.778
P-glycoprotein inhibitor IIInhibitor0.6802
Renal organic cation transporterNon-inhibitor0.6822
CYP450 2C9 substrateNon-substrate0.7289
CYP450 2D6 substrateNon-substrate0.7984
CYP450 3A4 substrateSubstrate0.707
CYP450 1A2 substrateNon-inhibitor0.8801
CYP450 2C9 substrateNon-inhibitor0.8903
CYP450 2D6 substrateNon-inhibitor0.9166
CYP450 2C19 substrateNon-inhibitor0.8855
CYP450 3A4 substrateNon-inhibitor0.88
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8541
Ames testNon AMES toxic0.6225
CarcinogenicityNon-carcinogens0.684
BiodegradationNot ready biodegradable0.9618
Rat acute toxicity2.5848 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7692
hERG inhibition (predictor II)Inhibitor0.5084
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage formsNot Available
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 mg/mLALOGPS
logP0.65ALOGPS
logP-1.4ChemAxon
logS-7.6ALOGPS
Physiological Charge2ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area59.08 Å2ChemAxon
Rotatable Bond Count17ChemAxon
Refractivity185.71 m3·mol-1ChemAxon
Polarizability64.49 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
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
ATC CodesS01EB04
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
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