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Identification
NameDemecarium
Accession NumberDB00944  (APRD00905)
TypeSmall Molecule
GroupsApproved
DescriptionDemecarium 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
Demecarium
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not 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
UNIIILP8XJ8R5K
CAS numberNot Available
WeightAverage: 556.7797
Monoisotopic: 556.398856172
Chemical FormulaC32H52N4O4
InChI KeyInChIKey=RWZVPVOZTJJMNU-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.
Related Articles
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 inhibitorNon-inhibitor0.8903
CYP450 2D6 inhibitorNon-inhibitor0.9166
CYP450 2C19 inhibitorNon-inhibitor0.8855
CYP450 3A4 inhibitorNon-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
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
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 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:12641839 ]
  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:7887518 ]
  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:8430939 ]
External Links
ATC CodesS01EB04
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
4-AndrostenedioneThe risk or severity of adverse effects can be increased when 4-Androstenedione is combined with Demecarium.
AcebutololDemecarium may increase the bradycardic activities of Acebutolol.
AcetylcholineThe risk or severity of adverse effects can be increased when Demecarium is combined with Acetylcholine.
AclidiniumThe therapeutic efficacy of Aclidinium can be decreased when used in combination with Demecarium.
AlclometasoneThe risk or severity of adverse effects can be increased when Alclometasone is combined with Demecarium.
AldosteroneThe risk or severity of adverse effects can be increased when Aldosterone is combined with Demecarium.
AlprenololDemecarium may increase the bradycardic activities of Alprenolol.
AmcinonideThe risk or severity of adverse effects can be increased when Amcinonide is combined with Demecarium.
Anisotropine MethylbromideThe therapeutic efficacy of Anisotropine Methylbromide can be decreased when used in combination with Demecarium.
ArecolineThe risk or severity of adverse effects can be increased when Demecarium is combined with Arecoline.
ArotinololDemecarium may increase the bradycardic activities of Arotinolol.
AtenololDemecarium may increase the bradycardic activities of Atenolol.
Atracurium besylateThe therapeutic efficacy of Atracurium besylate can be decreased when used in combination with Demecarium.
AtropineThe therapeutic efficacy of Atropine can be decreased when used in combination with Demecarium.
Beclomethasone dipropionateThe risk or severity of adverse effects can be increased when Beclomethasone dipropionate is combined with Demecarium.
BefunololDemecarium may increase the bradycardic activities of Befunolol.
BenactyzineThe therapeutic efficacy of Benactyzine can be decreased when used in combination with Demecarium.
BenzatropineThe therapeutic efficacy of Benzatropine can be decreased when used in combination with Demecarium.
BetamethasoneThe risk or severity of adverse effects can be increased when Betamethasone is combined with Demecarium.
BetaxololDemecarium may increase the bradycardic activities of Betaxolol.
BethanecholThe risk or severity of adverse effects can be increased when Demecarium is combined with Bethanechol.
BevantololDemecarium may increase the bradycardic activities of Bevantolol.
BiperidenThe therapeutic efficacy of Biperiden can be decreased when used in combination with Demecarium.
BisoprololDemecarium may increase the bradycardic activities of Bisoprolol.
BopindololDemecarium may increase the bradycardic activities of Bopindolol.
BudesonideThe risk or severity of adverse effects can be increased when Budesonide is combined with Demecarium.
BufuralolDemecarium may increase the bradycardic activities of Bufuralol.
BupranololDemecarium may increase the bradycardic activities of Bupranolol.
CarbacholThe risk or severity of adverse effects can be increased when Demecarium is combined with Carbachol.
CarteololDemecarium may increase the bradycardic activities of Carteolol.
CarvedilolDemecarium may increase the bradycardic activities of Carvedilol.
CeliprololDemecarium may increase the bradycardic activities of Celiprolol.
CevimelineThe risk or severity of adverse effects can be increased when Demecarium is combined with Cevimeline.
ChlorphenoxamineThe therapeutic efficacy of Chlorphenoxamine can be decreased when used in combination with Demecarium.
CiclesonideThe risk or severity of adverse effects can be increased when Ciclesonide is combined with Demecarium.
Clobetasol propionateThe risk or severity of adverse effects can be increased when Clobetasol propionate is combined with Demecarium.
ClocortoloneThe risk or severity of adverse effects can be increased when Clocortolone is combined with Demecarium.
Cortisone acetateThe risk or severity of adverse effects can be increased when Cortisone acetate is combined with Demecarium.
CyclopentolateThe therapeutic efficacy of Cyclopentolate can be decreased when used in combination with Demecarium.
DarifenacinThe therapeutic efficacy of Darifenacin can be decreased when used in combination with Demecarium.
DehydroepiandrosteroneThe risk or severity of adverse effects can be increased when Dehydroepiandrosterone is combined with Demecarium.
dehydroepiandrosterone sulfateThe risk or severity of adverse effects can be increased when dehydroepiandrosterone sulfate is combined with Demecarium.
DesloratadineThe therapeutic efficacy of Desloratadine can be decreased when used in combination with Demecarium.
DesoximetasoneThe risk or severity of adverse effects can be increased when Desoximetasone is combined with Demecarium.
Desoxycorticosterone acetateThe risk or severity of adverse effects can be increased when Desoxycorticosterone acetate is combined with Demecarium.
DexamethasoneThe risk or severity of adverse effects can be increased when Dexamethasone is combined with Demecarium.
Dexamethasone isonicotinateThe risk or severity of adverse effects can be increased when Dexamethasone isonicotinate is combined with Demecarium.
DexetimideThe therapeutic efficacy of Dexetimide can be decreased when used in combination with Demecarium.
DicyclomineThe therapeutic efficacy of Dicyclomine can be decreased when used in combination with Demecarium.
DiflorasoneThe risk or severity of adverse effects can be increased when Diflorasone is combined with Demecarium.
DifluocortoloneThe risk or severity of adverse effects can be increased when Difluocortolone is combined with Demecarium.
DifluprednateThe risk or severity of adverse effects can be increased when Difluprednate is combined with Demecarium.
DipyridamoleThe therapeutic efficacy of Demecarium can be decreased when used in combination with Dipyridamole.
EPIBATIDINEThe risk or severity of adverse effects can be increased when Demecarium is combined with EPIBATIDINE.
EquileninThe risk or severity of adverse effects can be increased when Equilenin is combined with Demecarium.
EquilinThe risk or severity of adverse effects can be increased when Equilin is combined with Demecarium.
EsmololDemecarium may increase the bradycardic activities of Esmolol.
EstroneThe risk or severity of adverse effects can be increased when Estrone is combined with Demecarium.
EthopropazineThe therapeutic efficacy of Ethopropazine can be decreased when used in combination with Demecarium.
FesoterodineThe therapeutic efficacy of Fesoterodine can be decreased when used in combination with Demecarium.
FludrocortisoneThe risk or severity of adverse effects can be increased when Fludrocortisone is combined with Demecarium.
FlumethasoneThe risk or severity of adverse effects can be increased when Flumethasone is combined with Demecarium.
FlunisolideThe risk or severity of adverse effects can be increased when Flunisolide is combined with Demecarium.
Fluocinolone AcetonideThe risk or severity of adverse effects can be increased when Fluocinolone Acetonide is combined with Demecarium.
FluocinonideThe risk or severity of adverse effects can be increased when Fluocinonide is combined with Demecarium.
FluocortoloneThe risk or severity of adverse effects can be increased when Fluocortolone is combined with Demecarium.
FluorometholoneThe risk or severity of adverse effects can be increased when Fluorometholone is combined with Demecarium.
FluprednideneThe risk or severity of adverse effects can be increased when Fluprednidene is combined with Demecarium.
FluprednisoloneThe risk or severity of adverse effects can be increased when Fluprednisolone is combined with Demecarium.
FlurandrenolideThe risk or severity of adverse effects can be increased when Flurandrenolide is combined with Demecarium.
Fluticasone furoateThe risk or severity of adverse effects can be increased when Fluticasone furoate is combined with Demecarium.
Fluticasone PropionateThe risk or severity of adverse effects can be increased when Fluticasone Propionate is combined with Demecarium.
Gallamine TriethiodideThe therapeutic efficacy of Gallamine Triethiodide can be decreased when used in combination with Demecarium.
GlycopyrroniumThe therapeutic efficacy of Glycopyrronium can be decreased when used in combination with Demecarium.
GTS-21The risk or severity of adverse effects can be increased when Demecarium is combined with GTS-21.
HexamethoniumThe therapeutic efficacy of Hexamethonium can be decreased when used in combination with Demecarium.
HomatropineThe therapeutic efficacy of Homatropine can be decreased when used in combination with Demecarium.
HydrocortisoneThe risk or severity of adverse effects can be increased when Hydrocortisone is combined with Demecarium.
HyoscyamineThe therapeutic efficacy of Hyoscyamine can be decreased when used in combination with Demecarium.
IndenololDemecarium may increase the bradycardic activities of Indenolol.
Ipratropium bromideThe therapeutic efficacy of Ipratropium bromide can be decreased when used in combination with Demecarium.
LabetalolDemecarium may increase the bradycardic activities of Labetalol.
LobelineThe risk or severity of adverse effects can be increased when Demecarium is combined with Lobeline.
MecamylamineThe therapeutic efficacy of Mecamylamine can be decreased when used in combination with Demecarium.
MedrysoneThe risk or severity of adverse effects can be increased when Medrysone is combined with Demecarium.
MelengestrolThe risk or severity of adverse effects can be increased when Melengestrol is combined with Demecarium.
MethacholineThe risk or severity of adverse effects can be increased when Demecarium is combined with Methacholine.
MethanthelineThe therapeutic efficacy of Methantheline can be decreased when used in combination with Demecarium.
MethylprednisoloneThe risk or severity of adverse effects can be increased when Methylprednisolone is combined with Demecarium.
MetixeneThe therapeutic efficacy of Metixene can be decreased when used in combination with Demecarium.
MetoprololDemecarium may increase the bradycardic activities of Metoprolol.
MivacuriumDemecarium may decrease the neuromuscular blocking activities of Mivacurium.
MometasoneThe risk or severity of adverse effects can be increased when Mometasone is combined with Demecarium.
N-butylscopolammonium bromideThe therapeutic efficacy of N-butylscopolammonium bromide can be decreased when used in combination with Demecarium.
NadololDemecarium may increase the bradycardic activities of Nadolol.
NicotineThe risk or severity of adverse effects can be increased when Demecarium is combined with Nicotine.
Nicotine bitartrateThe risk or severity of adverse effects can be increased when Demecarium is combined with Nicotine bitartrate.
NVA237The therapeutic efficacy of NVA237 can be decreased when used in combination with Demecarium.
OrphenadrineThe therapeutic efficacy of Orphenadrine can be decreased when used in combination with Demecarium.
OxprenololDemecarium may increase the bradycardic activities of Oxprenolol.
OxybutyninThe therapeutic efficacy of Oxybutynin can be decreased when used in combination with Demecarium.
OxyphenoniumThe therapeutic efficacy of Oxyphenonium can be decreased when used in combination with Demecarium.
PancuroniumThe therapeutic efficacy of Pancuronium can be decreased when used in combination with Demecarium.
ParamethasoneThe risk or severity of adverse effects can be increased when Paramethasone is combined with Demecarium.
PenbutololDemecarium may increase the bradycardic activities of Penbutolol.
PentoliniumThe therapeutic efficacy of Pentolinium can be decreased when used in combination with Demecarium.
PilocarpineThe risk or severity of adverse effects can be increased when Demecarium is combined with Pilocarpine.
PindololDemecarium may increase the bradycardic activities of Pindolol.
PipecuroniumThe therapeutic efficacy of Pipecuronium can be decreased when used in combination with Demecarium.
PirenzepineThe therapeutic efficacy of Pirenzepine can be decreased when used in combination with Demecarium.
PractololDemecarium may increase the bradycardic activities of Practolol.
PrednicarbateThe risk or severity of adverse effects can be increased when Prednicarbate is combined with Demecarium.
PrednisoloneThe risk or severity of adverse effects can be increased when Prednisolone is combined with Demecarium.
PrednisoneThe risk or severity of adverse effects can be increased when Prednisone is combined with Demecarium.
PregnenoloneThe risk or severity of adverse effects can be increased when Pregnenolone is combined with Demecarium.
ProcyclidineThe therapeutic efficacy of Procyclidine can be decreased when used in combination with Demecarium.
PropanthelineThe therapeutic efficacy of Propantheline can be decreased when used in combination with Demecarium.
PropranololDemecarium may increase the bradycardic activities of Propranolol.
QuinidineThe therapeutic efficacy of Quinidine can be decreased when used in combination with Demecarium.
RapacuroniumDemecarium may decrease the neuromuscular blocking activities of Rapacuronium.
RimexoloneThe risk or severity of adverse effects can be increased when Rimexolone is combined with Demecarium.
ScopolamineThe therapeutic efficacy of Scopolamine can be decreased when used in combination with Demecarium.
Scopolamine butylbromideThe therapeutic efficacy of Scopolamine butylbromide can be decreased when used in combination with Demecarium.
SolifenacinThe therapeutic efficacy of Solifenacin can be decreased when used in combination with Demecarium.
SotalolDemecarium may increase the bradycardic activities of Sotalol.
SuccinylcholineThe serum concentration of Succinylcholine can be increased when it is combined with Demecarium.
TimololDemecarium may increase the bradycardic activities of Timolol.
TiotropiumThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Demecarium.
TixocortolThe risk or severity of adverse effects can be increased when Tixocortol is combined with Demecarium.
TolterodineThe therapeutic efficacy of Tolterodine can be decreased when used in combination with Demecarium.
TriamcinoloneThe risk or severity of adverse effects can be increased when Triamcinolone is combined with Demecarium.
TrihexyphenidylThe therapeutic efficacy of Trihexyphenidyl can be decreased when used in combination with Demecarium.
TrimethaphanThe therapeutic efficacy of Trimethaphan can be decreased when used in combination with Demecarium.
TropicamideThe therapeutic efficacy of Tropicamide can be decreased when used in combination with Demecarium.
TrospiumThe therapeutic efficacy of Trospium can be decreased when used in combination with Demecarium.
TubocurarineThe therapeutic efficacy of Tubocurarine can be decreased when used in combination with Demecarium.
UmeclidiniumThe therapeutic efficacy of Umeclidinium can be decreased when used in combination with Demecarium.
VareniclineThe risk or severity of adverse effects can be increased when Demecarium is combined with Varenicline.
VecuroniumThe therapeutic efficacy of Vecuronium can be decreased when used in combination with Demecarium.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Serine hydrolase activity
Specific Function:
Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.
Gene Name:
ACHE
Uniprot ID:
P22303
Molecular Weight:
67795.525 Da
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:12641839 ]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Identical protein binding
Specific Function:
Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
Gene Name:
BCHE
Uniprot ID:
P06276
Molecular Weight:
68417.575 Da
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:7196602 ]
  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:8430939 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23