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Identification
Name Demecarium
Accession Number DB00944 (APRD00905)
Type small molecule
Groups approved
Description

Demecarium bromid 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
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Synonyms
Demecarium bromide
Salts Not Available
Brand names Not Available
Brand mixtures Not Available
Categories
  • Miotics
  • Cholinergic Agents
CAS number 56-94-0
Weight Average: 556.7797
Monoisotopic: 556.398856172
Chemical Formula C32H52N4O4
InChI Key InChIKey=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
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Not Available
Classes Not Available
Substructures Not Available
Pharmacology
Indication For the topical treatment of chronic open-angle glaucoma.
Pharmacodynamics Demecarium 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 action Demecarium 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.
Absorption Not Available
Volume of distribution Not Available
Protein binding Not Available
Metabolism Not Available
Route of elimination Not Available
Half life Not Available
Clearance Not Available
Toxicity The 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
Pathways Not Available
Pharmacoeconomics
Manufacturers Not Available
Packagers
Dosage forms
Form Route Strength
Solution Ophthalmic
Prices Not Available
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
logP -1.75 Not Available
Predicted Properties
Property Value Source
water solubility 1.69e-05 g/l ALOGPS
logP 0.65 ALOGPS
logP -1.4 ChemAxon
logS -7.6 ALOGPS
physiological charge 2 ChemAxon
hydrogen acceptor count 2 ChemAxon
hydrogen donor count 0 ChemAxon
polar surface area 59.08 ChemAxon
rotatable bond count 17 ChemAxon
refractivity 185.71 ChemAxon
polarizability 64.49 ChemAxon
References
Synthesis Reference Not Available
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
Resource Link
KEGG Drug D00667 Link_out
PubChem Compound 5965 Link_out
PubChem Substance 46507824 Link_out
Therapeutic Targets Database DAP000894 Link_out
PharmGKB PA164745610 Link_out
RxList http://www.rxlist.com/cgi/generic2/demecarium.htm Link_out
Drugs.com http://www.drugs.com/mtm/demecarium-bromide-ophthalmic.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Demecarium_bromide Link_out
ATC Codes
  • S01EB04
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Tacrine The acetylcholinesterase inhibitor, Tacrine, may increase the adverse/toxic effects of Demcarium, a cholinergic agonist. Monitor for increased cholinergic effects and toxicity.
Food Interactions Not Available
Targets

1. Acetylcholinesterase

Pharmacological action: yes
Actions: inhibitor

Rapidly hydrolyzes choline released into the synapse

Organism class: human
UniProt ID: P22303 Link_out
Gene: ACHE Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown
Actions: inhibitor

An acylcholine + H(2)O = choline + a carboxylate

Organism class: human
UniProt ID: P06276 Link_out
Gene: BCHE Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19