Identification

Name
Carbamoylcholine
Commonly known or available as Carbachol
Accession Number
DB00411  (APRD00845, DB02487)
Type
Small Molecule
Groups
Approved
Description

A slowly hydrolyzed cholinergic agonist that acts at both muscarinic and nicotinic receptors.

Structure
Thumb
Synonyms
  • Carbacholine
  • carbacol
  • Carbamylcholine
  • Choline carbamate
Product Ingredients
IngredientUNIICASInChI Key
Carbamoylcholine chloride8Y164V895Y51-83-2AIXAANGOTKPUOY-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CarbacholTablet2 mgOralMylan Pharmaceuticals1995-12-312015-11-03Canada
Carbachol Injection Liq Sc 0.25mg/mlLiquid.25 mgSubcutaneousBioniche Pharma (Canada) Ltd1995-12-312014-11-24Canada
Carbachol Intraocular Solution 0.01%Liquid0.1 mgIntraocularSabex IncNot applicableNot applicableCanada
Carbachol Tab 2mgTablet2 mgOralAllen & Hanburys A Glaxo Canada Ltd. Co.1951-12-311996-09-10Canada
CarbastatInjection, solution0.1 mg/1mLIntraocularNovartis Ophthalmics2006-09-19Not applicableUs
CarbastatSolution0.01 %IntraocularNovartis Ophthalmics Novartis Pharmaceuticals (Canada) Inc1996-10-222004-07-13Canada
Isopto Carbachol 1.5%Liquid1.5 %OphthalmicAlcon, Inc.1951-12-312012-08-14Canada
Isopto Carbachol 3%Liquid3 %OphthalmicAlcon, Inc.1951-12-312013-02-28Canada
MiostatSolution0.1 mg/1mLOphthalmicAlcon, Inc.1974-04-15Not applicableUs
Miostat Ophthalmic Liq 0.01%Solution.01 %IntraocularAlcon, Inc.1980-12-31Not applicableCanada
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Isopto CarbacholCarbamoylcholine chloride (15 mg/1mL)SolutionOphthalmicAlcon, Inc.1981-06-192012-09-28Us
Isopto CarbacholCarbamoylcholine chloride (30 mg/1mL)SolutionOphthalmicAlcon, Inc.1981-06-192012-09-28Us
International/Other Brands
Carboptic (NutraMax) / Isopto Carbachol (Alcon Laboratories, Inc.) / Mioticol (Farmigea)
Categories
UNII
54Z8M50D6Q
CAS number
462-58-8
Weight
Average: 147.1955
Monoisotopic: 147.113352734
Chemical Formula
C6H15N2O2
InChI Key
VPJXQGSRWJZDOB-UHFFFAOYSA-O
InChI
InChI=1S/C6H14N2O2/c1-8(2,3)4-5-10-6(7)9/h4-5H2,1-3H3,(H-,7,9)/p+1
IUPAC Name
2-(trimethylazaniumyl)ethyl carbamate
SMILES
C[N+](C)(C)CCOC(N)=O

Pharmacology

Indication

Primarily used in the treatment of glaucoma, but is also used during ophthalmic surgery.

Associated Conditions
Pharmacodynamics

Carbachol is a potent cholinergic (parasympathomimetic) agent which produces constriction of the iris and ciliary body resulting in reduction in intraocular pressure. The exact mechanism by which carbachol lowers intraocular pressure is not precisely known. In the cat and rat, carbachol is well-known for its ability to induce rapid eye movement (REM) sleep when microinjected into the pontine reticular formation. Carbachol elicits this REM sleep-like state via activation of postsynaptic muscarinic cholinergic receptors (mAChRs).

Mechanism of action

Carbachol is a parasympathomimetic that stimulates both muscarinic and nicotinic receptors. In topical ocular and intraocular administration its principal effects are miosis and increased aqueous humour outflow.

TargetActionsOrganism
AMuscarinic acetylcholine receptor M1
agonist
Human
AMuscarinic acetylcholine receptor M2
agonist
Human
ANeuronal acetylcholine receptor subunit alpha-2
agonist
Human
UAcetylcholinesteraseNot AvailableHuman
UMuscarinic acetylcholine receptor M3Not AvailableHuman
UMuscarinic acetylcholine receptor M4Not AvailableHuman
Absorption

Not well absorbed in the gastro-intestinal tract, and does not cross the blood-brain barrier.

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

Oral, mouse: LD50 = 15 mg/kg; Oral, rat: LD50 = 40 mg/kg.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
1,10-PhenanthrolineThe risk or severity of adverse effects can be increased when 1,10-Phenanthroline is combined with Carbamoylcholine.
AcebutololThe risk or severity of adverse effects can be increased when Acebutolol is combined with Carbamoylcholine.
AlprenololThe risk or severity of adverse effects can be increased when Alprenolol is combined with Carbamoylcholine.
AmbenoniumThe risk or severity of adverse effects can be increased when Ambenonium is combined with Carbamoylcholine.
AmikacinThe therapeutic efficacy of Carbamoylcholine can be decreased when used in combination with Amikacin.
AnisodamineThe risk or severity of adverse effects can be increased when Anisodamine is combined with Carbamoylcholine.
ApramycinThe therapeutic efficacy of Carbamoylcholine can be decreased when used in combination with Apramycin.
ArbekacinThe therapeutic efficacy of Carbamoylcholine can be decreased when used in combination with Arbekacin.
ArotinololThe risk or severity of adverse effects can be increased when Arotinolol is combined with Carbamoylcholine.
AtenololThe risk or severity of adverse effects can be increased when Atenolol is combined with Carbamoylcholine.
Food Interactions
Not Available

References

Synthesis Reference

Major, R.T. and Bonnett, H.T.; U.S. Patent 2,374,367; April 24,1945; assigned to Merck & Co., Inc.

General References
Not Available
External Links
Human Metabolome Database
HMDB0014555
KEGG Drug
D00524
PubChem Compound
5831
PubChem Substance
46509115
ChemSpider
2454
BindingDB
50004656
ChEBI
3385
ChEMBL
CHEMBL965
Therapeutic Targets Database
DAP000347
PharmGKB
PA448784
IUPHAR
298
Guide to Pharmacology
GtP Drug Page
HET
CCE
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Carbachol
ATC Codes
N07AB01 — CarbacholS01EB02 — Carbachol
AHFS Codes
  • 52:40.20 — Miotics
  • 12:04.00 — Parasympathomemetic (Cholinergic) Agents
PDB Entries
1uv6
FDA label
Download (79.4 KB)
MSDS
Download (64.9 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
Not AvailableCompletedBasic ScienceHeadaches1
Not AvailableCompletedScreeningHeadaches1

Pharmacoeconomics

Manufacturers
  • Pharmafair inc
  • Novartis pharmaceuticals corp
  • Alcon laboratories inc
Packagers
  • Alcon Laboratories
  • Novartis AG
  • OMJ Pharmaceuticals
  • Physicians Total Care Inc.
  • Professional Co.
Dosage forms
FormRouteStrength
LiquidSubcutaneous.25 mg
LiquidIntraocular0.1 mg
TabletOral2 mg
Injection, solutionIntraocular0.1 mg/1mL
SolutionIntraocular0.01 %
SolutionOphthalmic15 mg/1mL
SolutionOphthalmic30 mg/1mL
LiquidOphthalmic1.5 %
LiquidOphthalmic3 %
SolutionOphthalmic0.1 mg/1mL
SolutionIntraocular.01 %
Prices
Unit descriptionCostUnit
Isopto Carbachol 3% Solution 15ml Bottle61.76USD bottle
Carbachol 99% powder53.1USD g
Isopto Carbachol 1.5% Solution 15ml Bottle48.64USD bottle
Isopto Carbachol 1.5% Solution 30ml Bottle44.99USD bottle
Miostat vial32.4USD ml
Isopto carbachol 3% drops3.51USD ml
Isopto carbachol 1.5% drops3.07USD ml
Isopto Carbachol 3 % Solution0.91USD ml
Isopto Carbachol 1.5 % Solution0.76USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)208-210Major, R.T. and Bonnett, H.T.; U.S. Patent 2,374,367; April 24,1945; assigned to Merck & Co., Inc.
water solubility1 g/mlNot Available
logP-3.78Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.706 mg/mLALOGPS
logP-3ALOGPS
logP-4.6ChemAxon
logS-2.4ALOGPS
pKa (Strongest Acidic)15.23ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area52.32 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity50.02 m3·mol-1ChemAxon
Polarizability16.02 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.7542
Blood Brain Barrier+0.9727
Caco-2 permeable+0.5111
P-glycoprotein substrateNon-substrate0.6062
P-glycoprotein inhibitor INon-inhibitor0.9569
P-glycoprotein inhibitor IINon-inhibitor0.9545
Renal organic cation transporterNon-inhibitor0.8526
CYP450 2C9 substrateNon-substrate0.7825
CYP450 2D6 substrateNon-substrate0.7825
CYP450 3A4 substrateSubstrate0.5643
CYP450 1A2 substrateNon-inhibitor0.8329
CYP450 2C9 inhibitorNon-inhibitor0.8895
CYP450 2D6 inhibitorNon-inhibitor0.9204
CYP450 2C19 inhibitorNon-inhibitor0.8551
CYP450 3A4 inhibitorNon-inhibitor0.9515
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9416
Ames testNon AMES toxic0.667
CarcinogenicityNon-carcinogens0.5998
BiodegradationNot ready biodegradable0.9151
Rat acute toxicity2.6763 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9765
hERG inhibition (predictor II)Non-inhibitor0.8719
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (7.39 KB)
Spectra
Not Available

Taxonomy

Classification
Not classified

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Phosphatidylinositol phospholipase c activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM1
Uniprot ID
P11229
Uniprot Name
Muscarinic acetylcholine receptor M1
Molecular Weight
51420.375 Da
References
  1. Weiner DM, Goodman MW, Colpitts TM, Feddock MA, Duggento KL, Nash NR, Levey AI, Brann MR: Functional screening of drug target genes: m1 muscarinic acetylcholine receptor phenotypes in degenerative dementias. Am J Pharmacogenomics. 2004;4(2):119-28. [PubMed:15059034]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
G-protein coupled acetylcholine receptor activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM2
Uniprot ID
P08172
Uniprot Name
Muscarinic acetylcholine receptor M2
Molecular Weight
51714.605 Da
References
  1. Peter JC, Wallukat G, Tugler J, Maurice D, Roegel JC, Briand JP, Hoebeke J: Modulation of the M2 muscarinic acetylcholine receptor activity with monoclonal anti-M2 receptor antibody fragments. J Biol Chem. 2004 Dec 31;279(53):55697-706. Epub 2004 Oct 14. [PubMed:15485827]
  2. May LT, Lin Y, Sexton PM, Christopoulos A: Regulation of M2 muscarinic acetylcholine receptor expression and signaling by prolonged exposure to allosteric modulators. J Pharmacol Exp Ther. 2005 Jan;312(1):382-90. Epub 2004 Aug 27. [PubMed:15333678]
  3. Sawatzky DA, Kingham PJ, Durcan N, McLean WG, Costello RW: Eosinophil-induced release of acetylcholine from differentiated cholinergic nerve cells. Am J Physiol Lung Cell Mol Physiol. 2003 Dec;285(6):L1296-304. Epub 2003 Aug 29. [PubMed:12948933]
  4. Sterin-Borda L, Joensen L, Bayo-Hanza C, Esteva M, Borda E: Therapeutic use of muscarinic acetylcholine receptor peptide to prevent mice chagasic cardiac dysfunction. J Mol Cell Cardiol. 2002 Dec;34(12):1645-54. [PubMed:12505062]
  5. Zuchner T, Schliebs R, Perez-Polo JR: Down-regulation of muscarinic acetylcholine receptor M2 adversely affects the expression of Alzheimer's disease-relevant genes and proteins. J Neurochem. 2005 Oct;95(1):20-32. [PubMed:16181410]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Drug binding
Specific Function
After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
Gene Name
CHRNA2
Uniprot ID
Q15822
Uniprot Name
Neuronal acetylcholine receptor subunit alpha-2
Molecular Weight
59764.82 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. An MC, Lin W, Yang J, Dominguez B, Padgett D, Sugiura Y, Aryal P, Gould TW, Oppenheim RW, Hester ME, Kaspar BK, Ko CP, Lee KF: Acetylcholine negatively regulates development of the neuromuscular junction through distinct cellular mechanisms. Proc Natl Acad Sci U S A. 2010 Jun 8;107(23):10702-7. doi: 10.1073/pnas.1004956107. Epub 2010 May 24. [PubMed:20498043]
  4. 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
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
Uniprot Name
Acetylcholinesterase
Molecular Weight
67795.525 Da
References
  1. Rosenberry TL, Sonoda LK, Dekat SE, Cusack B, Johnson JL: Monitoring the reaction of carbachol with acetylcholinesterase by thioflavin T fluorescence and acetylthiocholine hydrolysis. Chem Biol Interact. 2008 Sep 25;175(1-3):235-41. doi: 10.1016/j.cbi.2008.06.002. Epub 2008 Jun 17. [PubMed:18602908]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Receptor activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM3
Uniprot ID
P20309
Uniprot Name
Muscarinic acetylcholine receptor M3
Molecular Weight
66127.445 Da
References
  1. Stewart GD, Sexton PM, Christopoulos A: Prediction of functionally selective allosteric interactions at an M3 muscarinic acetylcholine receptor mutant using Saccharomyces cerevisiae. Mol Pharmacol. 2010 Aug;78(2):205-14. doi: 10.1124/mol.110.064253. Epub 2010 May 13. [PubMed:20466821]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Guanyl-nucleotide exchange factor activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM4
Uniprot ID
P08173
Uniprot Name
Muscarinic acetylcholine receptor M4
Molecular Weight
53048.65 Da
References
  1. Jakubik J, Bacakova L, El-Fakahany EE, Tucek S: Positive cooperativity of acetylcholine and other agonists with allosteric ligands on muscarinic acetylcholine receptors. Mol Pharmacol. 1997 Jul;52(1):172-9. [PubMed:9224827]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Phospholipase a2 activity
Specific Function
Selectively hydrolyzes arachidonyl phospholipids in the sn-2 position releasing arachidonic acid. Together with its lysophospholipid activity, it is implicated in the initiation of the inflammatory...
Gene Name
PLA2G4A
Uniprot ID
P47712
Uniprot Name
Cytosolic phospholipase A2
Molecular Weight
85238.2 Da
References
  1. Konrad RJ, Jolly YC, Major C, Wolf BA: Carbachol stimulation of phospholipase A2 and insulin secretion in pancreatic islets. Biochem J. 1992 Oct 1;287 ( Pt 1):283-90. [PubMed:1417779]
  2. Enyedi P, Fredholm BB: Calcium-dependent enhancement by carbachol of the VIP-induced cyclic AMP accumulation in cat submandibular gland. Acta Physiol Scand. 1984 Apr;120(4):523-8. [PubMed:6091414]
  3. Grosfils K, Gomez F, Dehaye JP: Inhibition by mepacrine and amylase secretion from intact and permeabilized rat pancreatic acini. Biochem Biophys Res Commun. 1992 Apr 15;184(1):408-13. [PubMed:1373616]
  4. Ying Z, Tojo H, Nonaka Y, Okamoto M: Cloning and expression of phospholipase A2 from guinea pig gastric mucosa, its induction by carbachol and secretion in vivo. Eur J Biochem. 1993 Jul 1;215(1):91-7. [PubMed:8344290]
  5. Strosznajder J, Strosznajder RP: Guanine nucleotides and fluoride enhance carbachol-mediated arachidonic acid release from phosphatidylinositol. Evidence for involvement of GTP-binding protein in phospholipase A2 activation. J Lipid Mediat. 1989 Jul-Aug;1(4):217-29. [PubMed:2519894]
  6. Hirasawa N, Santini F, Beaven MA: Activation of the mitogen-activated protein kinase/cytosolic phospholipase A2 pathway in a rat mast cell line. Indications of different pathways for release of arachidonic acid and secretory granules. J Immunol. 1995 May 15;154(10):5391-402. [PubMed:7730640]
  7. Strosznajder J, Samochocki M: Carbachol-stimulated release of arachidonic acid and eicosanoids from brain cortex synaptoneurosome lipids of adult and aged rats. Adv Exp Med Biol. 1992;318:251-8. [PubMed:1636494]

Drug created on June 13, 2005 07:24 / Updated on December 12, 2018 07:04