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Executive Summary Information

Compound Carbachol (Carbamylcholine)
Mechanisms Carbachol is a cholinergic agonist that stimulates both muscarinic and nicotinic receptor subtypes.
Comments Cardiomyocytes have historically been difficult to establish and maintain in cell culture, and it is desirable to monitor cell lines for the proper phenotypes. Carbachol will be used to demonstrate the appropriate response to cholinergic agonists.
Feedback Contact Gold Compound Working Group (GCWG)

Leadscope Id LS-53194
CAS 51-83-2
DrugBank DB00411
ChemSpider 5626
UNII 8Y164V895Y
ChEBI 3385
Pathway DBs
KEGG D00524
Assay DBs
PubChem CID 5831
Omics DBs
ToxCast Accepted yes
ToxBank Accepted yes
Approved on 2012-05-01
Target Cholinergic (parasympathomimetic) agent

In Vivo Data ? Compound Assessment
Adverse Events ? Limiting systemic toxicity generally reflects agonism of the parasympathetic nervous system:

Systemic reactions after chronic topical application to the eye or intraocular injection are rare and usually occur only with very frequent administration. Adverse systemic effects result from parasympathetic stimulation and the most common effects, especially in children, include nausea, vomiting, diarrhea, abdominal pain, and intestinal cramps.


-McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 92. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1992 (Plus Supplements 1992)., p. 1658

A 58-yr-old man developed esophageal rupture 2 hr after a subcutaneous injection of carbachol to relieve urinary retention.


-Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982., p. 1038
Toxicity Mechanisms ? Not applicable
Therapeutic Target ? Carbachol is a potent cholinergic (parasympathomimetic) agent which stimulates both muscarinic and nicotinic receptor subtypes. It is poorly absorbed orally and is used primarily topically on the eye to produce constriction of the iris and ciliary body resulting in reduction in intraocular pressure in the treatment of glaucoma.


-Table 13.2, Rang et al]. Rang & Dale's Pharmacology. 6th ed. Churchill Livingstone, 1997, ISBN: 978-0443069116

Stimulation of muscarinic receptors in the isolated atrium with carbachol decreases force of contraction (left atrium) or frequency (right atrium) in man and animals. In the ventricle of man and mouse, carbachol has little effect on basal cardiac function but greatly attenuates the contractile response to β-adrenoceptor stimulation, termed indirect inhibitory action.


-Endoh M (1999). “Muscarinic regulation of Ca2+ signaling in mammalian atrial and ventricular myocardium”, Eur J Pharmacol 375: 177-196.
-Jian-Bing Shen and Achilles J. PappaNO, “Carbachol Inhibits the L-Type Ca21 Current Augmented by 1,2-bis(2-Aminophenoxy)ethane-N,N,N9,N9-Tetraacetic Acid in Guinea Pig Ventricular Myocytes: Calcium-Sensitivity Hypothesis for Muscarinic Inhibition”, JPET 298:857–864, 2001.
-P Boknik, S Grote-Wessels, G Barteska, M Jiang, FU Müller, W Schmitz, J Neumann and L Birnbaumer, “Genetic disruption of G proteins, Gi2a or Goa, does not abolish inotropic and chronotropic effects of stimulating muscarinic cholinoceptors in atrium”, British Journal of Pharmacology (2009), 158, 1557–1564.

Acetylcholine released by the vagal nerve is proposed to induce hepatocyte proliferation. This effect is mimicked by carbachol in co-cultures of hepatocytes and vascular endothelial or smooth muscle cells.


-Ryoichi Yoshimura, Jun-ichi Arai, Yasuhisa Endo, “Vascular endothelial cells and smooth muscle cells mediate carbacholinduced hepatic cell proliferation via muscarinic receptors and IP3/PKC signaling cascades”, Cell Biology International 33 (2009) 516e523.

PK-ADME ? Compound Assessment
PK parameters ? Not applicable
Therapeutic window ?
  • Oral, mouse LD50 = 5 mg/kg
  • IV, mouse LD50 = 0.3 mg/kg


-Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989., p. 268.
  • Oral, mouse: LD50 = 15 mg/kg
  • Oral, rat: LD50 = 40 mg/kg


Metabolically activated ? Carbachol, which is an unsubstituted carbamyl ester, is totally resistant to hydrolysis by either acetylcholinesterase or nonspecific cholinesterases. Its systemic half-life is thus sufficiently long that it is distributed to areas of low blood flow. The parent compound is thought to be the active species, and metabolic activation has not been implicated in adverse events.


-Gilman, A.G., L.S.Goodman, and A. Gilman. (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 7th ed. New York: Macmillan Publishing Co., Inc., 1985., p. 101

Omics and IC50 Data ? Compound Assessment
Gene expression profiles known. ? Cell line stimulation with carbachol has been studied with microarrays, and carbachol has been included in a study to build a predictive model of cardiotoxicity.


-Thole Zuchner, Reinhard Schliebs, J. Regino Perez-Polo, “Down-regulation of muscarinic acetylcholine receptor M2 adversely affects the expression of Alzheimer's disease-relevant genes and proteins”, Journal of Neurochemistry 95: 20–32 (2005).
-S Bremer, AP Worth, M Paparella, K Bigot, E Kolossov, BK Fleischmann, J Hescheler, and M Balls, “Establishment of an in vitro reporter gene assay for developmental cardiac toxicity”, Toxicology in Vitro (2001) 15:215-223.
Proteomics profiles known. ? 39 proteins were up- and 29 were down-regulated in a proteomics study.


-Min Yu, Dong-mei Chen, Gang Hu, Hai Wang, “Proteomic response analysis of endothelial cells of human coronary artery to stimulation with carbachol”, Acta Pharmacol Sin 2004 Sep; 25 (9): 1124-1130. PMID 15339386
Metabonomics profiles known. ?
Fluxomics profiles known. ?
Epigenomics profiles known. ?
Observed IC50 for in vitro cellular efficacy. ? EC50/IC50 values in the range 0.0001 uM to 2 uM are reported for diverse assays in PubChem tabulations.


Observed IC50 for in vitro cellular toxicity studies. ? Not applicable

Physical Properties ? Compound Assessment
Accepted and listed within the ToxCast/Tox21 program. ? No - Not included in ToxCast Phase I and II Chemicals List
Substance stability. ?
Soluble in buffer solution at 30 times the in vitro IC50 for toxicity. ? Water: 1g/ml Sigma Aldrich (C4382)
  • estimated intrinsic solubility : 408.5491 mg/ml
  • estimated solubility in pure water at pH 6.06: 408.5492 mg/ml
  • estimated solubility in water at pH 7.4: 408.55 mg/ml

(Calculations performed using ACD/PhysChem v 12.0)

Solubility in DMSO 100 times buffer solubility. ? Soluble to 50 mM in DMSO Tocris Bioscience (2810)
Vessel binding properties. ?
Vapor pressure. (Non-volatile) ? Estimated vapor pressure (25°C): 6.46E-008 mmHg (Calculation performed using EPI Suite v4.1)

Authors of this ToxBank wiki page

David Bower, Egon Willighagen
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