nAChR and mAchR receptor (Ki = 10-10000 nM)

Serosal application of carbachol to T84 cell monolayers mounted in an Ussing chamber caused an immediate increase in short circuit current (Isc) that peaked within 5 min and declined rapidly thereafter, although a small increase in Isc persisted for approximately 30 min. The increase in Isc was detectable with 1 microM carbachol; half-maximal with 10 microM carbachol; and maximal with 100 microM carbachol. Unidirectional Na+ and Cl- flux measurements indicated that the increase in Isc was due to net Cl- secretion. Carbachol did not alter cellular cAMP, but caused a transient increase in free cytosolic Ca2+ ([Ca2+]i) from 117 +/- 7 nM to 160 +/- 15 nM. The carbachol-induced increase in Isc was potentiated by either prostaglandin E1 (PGE1) or vasoactive intestinal polypeptide (VIP), agents that act by increasing cAMP. Measurements of cAMP and [Ca2+]i indicated that the potentiated response was not due to changes in these second messengers. Studies of the effects of these agents on ion transport pathways indicated that carbachol, PGE1, or VIP each increased basolateral K+ efflux by activating two different K+ transport pathways on the basolateral membrane. The pathway activated by carbachol was not sensitive to barium, while that activated by PGE1 or VIP was; furthermore, their action on K+ efflux are additive. Our study indicates that carbachol causes Cl- secretion, and that this action may result from its ability to increase [Ca2+]i and basolateral K+ efflux. Carbachol's effect on Cl- secretion is greatly augmented in the presence of VIP or PGE1, which open a cAMP-sensitive Cl- channel on the apical membrane, accounting for a potentiated response [1].

CHOLINERGIC regulation of sleep and wakefulness was studied in freely moving rats locally infused with various doses of carbachol into the pontine reticular formation. Induction of REM sleep occurred when carbachol was infused specifically into the posterior oral pontine reticular nucleus (PnO). This effect was observed with 1–10 ng of carbachol, and lasted for at least 6 h. It was antagonized by atropine (100–200 ng) infused into the same site 15 min before carbachol (10 ng), indicating that REM sleep induction resulted from the stimulation of pontine muscarinic receptors. High doses of carbachol (500 ng) did not affect REM sleep but enhanced wakefulness. Cholinergic mechanisms within the PnO may play a critical role in the regulation of REM sleep in the rat [2].

Absorption, Distribution and Excretion
Topically applied carbachol has poor penetration into intact corneal epithelium; however, its penetration into the cornea can be significantly improved when used in combination with a wetting agent. Carbachol can be absorbed through intact skin. Metabolisms/Metabolites Carbachol is an unsubstituted carbamate ester, completely unaffected by hydrolysis by acetylcholinesterase or nonspecific cholinesterase; therefore, its half-life is long enough to distribute to areas with slow blood flow.

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
There is currently no information regarding the use of carbacholine eye drops during lactation. Due to its short half-life, it is unlikely to enter the infant's bloodstream and will not have any adverse effects on breastfed infants. ◉ Effects on Breastfed Infants
As of the revision date, no relevant published information was found. ◉ Effects on Lactation and Breast Milk
As of the revision date, no relevant published information was found regarding lactating women. In animal studies, cholinergic drugs can increase oxytocin release and have varying effects on serum prolactin levels. For mothers who have established lactation, prolactin levels may not affect their ability to breastfeed. Drug Interactions
Acetylcholine and methacholine can be hydrolyzed by acetylcholinesterase, and pre-administration of anticholinesterase drugs can significantly enhance their effects. The latter has an additive effect only with stable analogues such as carbacholine and betanicillin. The muscarinic-like effects of all such drugs can be selectively blocked by atropine through competitive occupation of cholinergic receptors on autonomic effector cells and secondary muscarinic receptors on autonomic ganglion cells. When used in combination with topical adrenaline, topical timolol, and/or systemically administered carbonic anhydrase inhibitors, the intraocular pressure-lowering effect of miotics may have an additive effect. While the clinical significance of miotics is not yet established, it has been reported that the miotic and/or intraocular pressure-lowering effects of miotics may be antagonized by long-term topical or systemic use of corticosteroids, systemic anticholinergics, antihistamines, meperidine, sympathomimetic drugs, and tricyclic antidepressants. The use of carbachol eye drops after the use of flurbiprofen eye drops may be ineffective; the pharmacological basis of this interference is unclear.
Concurrent use of… (e.g., belladonna alkaloids or cyclopenton) may interfere with the antihyperglycemic effect of carbachol; furthermore, concomitant use with carbachol may counteract the pupil-stimulating effects of these drugs.

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Non-human toxicity values
Oral LD50 in mice: 5 mg/kg
Intravenous LD50 in mice: 0.3 mg/kg

[1]. Mechanism of chloride secretion induced by carbachol in a colonic epithelial cell line.. J Clin Invest. 1986 Feb;77(2):348–354.
[2]. Induction of rapid eye movement sleep by carbachol infusion into the pontine reticular formation in the rat. Neuroreport. 1995 Feb 15;6(3):532-6.

Prismatic crystals or powder. Odorless, but develops a faint fatty amine odor when left to stand in an open container. A cholinergic parasympathomimetic drug, primarily used in large animals, especially horses, for abdominal pain. (EPA, 1998)
Carbachol is an ammonium salt and carbamate. It has a variety of pharmacological effects, including acting as a nicotinic acetylcholine receptor agonist, a muscarinic receptor agonist, a non-narcotic analgesic, a cardiotonic, and a miotic.
Carbachol is a synthetic choline ester and a positively charged quaternary ammonium compound. Carbachol is a parasympathomimetic drug that mimics the effects of acetylcholine on muscarinic and nicotinic receptors. When administered ocularly, it induces pupillary constriction, thereby lowering intraocular pressure, and is used to treat glaucoma. Carbachol is also used to stimulate urination by contracting the detrusor muscle. It may cause hypotension, bradycardia, nausea, vomiting, bronchospasm, and abdominal colic.
A slowly hydrolyzed cholinergic agonist that acts on muscarinic and nicotine receptors.
See also: carbamoylcholine (with the active moiety).

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Mechanism of Action
All miotics have similar pharmacological effects; their main differences lie in ocular and systemic absorption, duration of action, and intensity of action. Acetylcholine is an endogenous neurotransmitter that stimulates cholinergic receptors, producing muscarinic and nicotine-like effects. The effects of acetylcholine are transient. Pilocarpine, carbachol, and methacholine also directly stimulate cholinergic receptors; however, these drugs have a longer duration of action (several hours) than acetylcholine. There is evidence that carbachol also has a weaker anticholinesterase effect… Miotics can lower intraocular pressure in normal eyes and patients with glaucoma. The mechanisms by which these drugs lower intraocular pressure are not fully elucidated. In patients with open-angle (chronic simple, non-congestive) glaucoma, these drugs promote aqueous humor outflow, possibly through ciliary muscle contraction and trabecular meshwork dilation. ... Miotics reduce the activity of extraocular muscle converging muscles. ... Systemically absorbed miotics produce parasympathomimetic effects on multiple body systems. Carbachol selectively acts on gastrointestinal smooth muscle... Carbachol also retains significant nicotine activity, particularly on autonomic ganglia. Its peripheral and ganglion effects may be partly attributed to the release of endogenous acetylcholine from cholinergic fiber terminals. Cholinesterases (carbachol and betaniculline) enhance ureteral peristalsis, contract the bladder detrusor muscle, increase maximum voluntary voiding pressure, and reduce bladder capacity. Furthermore, the trigone and external sphincter relax. In animals with experimental spinal cord or sacral nerve root injuries, these drugs effectively empty neurogenic bladders. For more complete data on the mechanisms of action of carbachol chloride (7 types), please visit the HSDB record page.

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Therapeutic Uses
Non-narcotic analgesic; cardiotonic; cholinergic agonist; miotic; muscarinic receptor agonist; nicotinic receptor agonist; parasympathomimetic agent. 1% acetylcholine or 0.01% carbachol is used in cataract extraction and certain other anterior segment surgeries when rapid miosis is required; the effect of acetylcholine is transient. Carbachol (0.75% to 3.0%) has been used for the chronic treatment of non-congestive wide-angle glaucoma. Carbachol has also been used to treat postoperative intestinal atony and postoperative urinary retention, and can be administered subcutaneously or orally. In addition, carbachol can be used to terminate supraventricular paroxysmal tachycardia when all other measures are ineffective. Carbachol has a miotic effect, and its eye drops… have been used to lower intraocular pressure in patients with glaucoma… even in late-stage cases of solar blindness, symptoms are often relieved by retrobulbar injection of carbachol. Pilocarpine (sometimes also carbachol) is used for emergency preoperative treatment of acute (congestive) angle-closure glaucoma to lower intraocular pressure. For more complete data on the therapeutic uses of carbachol chloride (11 in total), please visit the HSDB record page. Drug Warnings Topical carbachol has the same toxicity as direct-acting miotics and should be treated with the usual precautions for miotic therapy. The manufacturer states that intraocular injection of carbachol does not produce the adverse effects of topical carbachol; however, bullous keratitis and iritis have been reported in some patients after cataract extraction.
Corneal edema may occur if excessive carbachol is injected into the anterior chamber, or if used in patients with impaired endothelial function (e.g., Fuchs' corneal endothelial dystrophy, corneal transplantation, cataract surgery requiring more manipulation than usual).
Carbachol eye drops are not recommended for patients with corneal abrasions due to the possibility of excessive absorption. Asthmatic patients who perform maximal breathing before inhaling carbachol may experience increased sensitivity to bronchoconstriction from carbachol.
These drugs can only be administered orally or subcutaneously to produce systemic effects; they can also be used topically in the eye. If administered intravenously or intramuscularly, their relative selectivity will not hold, and the incidence and severity of toxic side effects will be significantly increased. /Cholesterol Esters/
For more complete data on drug warnings for carbachol chloride (10 of them), please visit the HSDB records page.

C6H15CLN2O2

182.65

182.082

C, 39.46; H, 8.28; Cl, 19.41; N, 15.34; O, 17.52

51-83-2

51-83-2

5831

White to off-white solid powder

200-204 ºC

90°C(lit.)

1

3

4

11

117

0

O=C(OCC[N+](C)(C)C)N.[Cl-]

AIXAANGOTKPUOY-UHFFFAOYSA-N

InChI=1S/C6H14N2O2.ClH/c1-8(2,3)4-5-10-6(7)9/h4-5H2,1-3H3,(H-,7,9)1H

2-carbamoyloxyethyl(trimethyl)azaniumchloride

Carbastat; Carboptic; carbachol; 51-83-2; Carbamoylcholine chloride; Carbamylcholine chloride; Miostat; CARBACHOL CHLORIDE; Jestryl; Isopto Carbachol, Miostat, Carbamylcholine

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ≥ 50 mg/mL (~273.75 mM)
DMSO : ~6.4 mg/mL (~35.04 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)