Absorption, Distribution and Excretion
Topical carbachol penetrates intact corneal epithelium very poorly; combination with wetting agent ... greatly improves corneal penetration by the drug. ... Carbachol /is/ ... absorbed through intact skin.

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Metabolism / Metabolites
Carbachol, which is an unsubstituted carbamyl ester, is totally resistant to hydrolysis by either acetylcholinesterase or nonspecific cholinesterases; its half-life is thus sufficiently long that it is distributed to areas of low blood flow.

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
No information is available on the use of carbachol ophthalmic drops during breastfeeding. Because of its short half-life, it is not likely to reach the bloodstream of the infant or cause any adverse effects in breastfed infants.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information in nursing mothers was not found as of the revision date. In animals, cholinergic drugs increase oxytocin release, and have variable effects on serum prolactin. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.

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Interactions
Acetylcholine and methacholine are hydrolyzed by acetylcholinesterase and their effects are markedly enhanced by the prior administration of anticholinesterase agents. The latter drugs produce only additive effects with the stable analogs, carbachol and bethanechol. The muscarinic actions of all the drugs of this class are blocked selectively by atropine, through competitive occupation of cholinergic receptor sites on the autonomic effector cells and on the secondary muscarinic receptors of autonomic ganglion cells.
When used in conjunction with topical epinephrine, topical timolol, and/or systemically admin carbonic anhydrase inhibitiors, the effect of miotics in lowering intraocular pressure may be additive. /Miotics/
Although the clinical importance has not been established, the miotic and/or ocular hypotensive effects of miotics reportedly may be antagonized by long-term topical or systemic corticosteroid therapy, systemic anticholinergics, antihistamines, meperidine, sympathomimetics, & tricyclic antidepressants ... .
Ophthalmic carbachol may be ineffective when administred following ophthalmic flubiprofen; the pharmacologic basis for this interference is not known.
Concurrent use of ... /ophthalmic belladona alkaloids or cyclopentolate/ may interfere with the antiglucoma action of carbachol; also concurrent use with carbachol counteracts the myrdiatic effects of these medications ... .

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Non-Human Toxicity Values
LD50 Mouse oral 5 mg/kg
LD50 Mouse iv 0.3 mg/kg

: Fornai M, Pellegrini C, Antonioli L, Segnani C, Ippolito C, Barocelli E, Ballabeni V, Vegezzi G, Al Harraq Z, Blandini F, Levandis G, Cerri S, Blandizzi C, Bernardini N, Colucci R. Enteric dysfunctions in experimental Parkinson's disease: alterations of excitatory cholinergic neurotransmission regulating colonic motility in rats. J Pharmacol Exp Ther. 2015 Nov 18. pii: jpet.115.228510. [Epub ahead of print] PubMed PMID: 26582732.

Prismatic crystals or powder. Odorless, but develops a faint odor of aliphatic amine upon standing in an open container. Cholinergic, parasympathomimetic, used chiefly in large animals, especially for colic in the horse. (EPA, 1998)
Carbachol is an ammonium salt and a carbamate ester. It has a role as a nicotinic acetylcholine receptor agonist, a muscarinic agonist, a non-narcotic analgesic, a cardiotonic drug and a miotic.
Carbachol is a synthetic choline ester and a positively charged quaternary ammonium compound. Carbachol is a parasympathomimetic that mimics the effect of acetylcholine on both the muscarinic and nicotinic receptors. This drug is administered ocularly to induce miosis to reduce intraocular pressure in the treatment of glaucoma. Carbachol is also used to stimulate micturition by contraction of detrusor muscle. This drug may cause hypotension, bradycardia, nausea, vomiting, bronchospasm, and abdominal cramps.
A slowly hydrolyzed CHOLINERGIC AGONIST that acts at both MUSCARINIC RECEPTORS and NICOTINIC RECEPTORS.
See also: Carbamoylcholine (has active moiety).

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Mechanism of Action
The pharmacologic effects of all miotics are similar; they differ primarily in ocular and systemic absorption, duration of action and degree of effects. Acetylcholine, an endogenous mediator of nerve impulses, stimulates cholinergic receptors, resulting in muscarinic and nicotinic effects. The action of acetylcholine is transient. ... Pilocarpine, carbachol, and methacholine also directly stimulate cholinergic receptors; however, these drugs have a more prolonged duration of action (several hours) than does acetylcholine. There is some evidence that carbachol also has a weak anticholinesterase effect ... .
Miotics reduce intraocular pressure in normal and glaucomatous eyes. The mechanism of action of the drugs in lowering intraocular pressure has not been precisely determined. In patients with open-angle (chronic simple, noncongestive) glaucoma, the drugs facilitate aqueous humor outflow, apparently by causing contraction of the ciliary muscle and widening of the trabecular meshwork. ... Miotics decrease activity of extraocular muscles of convergence. ... Systemically absorbed miotics produce parasympathomimetic effects on various body systems. /Miotics/
/Carbachol acts/ ... with selectivity on the smooth muscle of the gastrointestinal tract ... Carbachol /also/ retains substantial nicotinic activity, particularly on autonomic ganglia. It is likely that both its peripheral and its ganglionic actions are due, in part, to the release of endogenous acetylcholine from the terminals of cholinergic fibers.
The choline esters /carbachol & bethanechol/ increase ureteral peristalsis, contract the detrusor muscle of the urinary bladder, increase the maximal voluntary voiding pressure, and decrease the capacity of the bladder. In addition, the trigone and external sphincter are relaxed. In animals with experimental lesions of the spinal cord or sacral roots, these drugs bring about satisfactory evacuation of the neurogenic bladder.
For more Mechanism of Action (Complete) data for CARBACHOL CHLORIDE (7 total), please visit the HSDB record page.

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Therapeutic Uses
Analgesics, Non-Narcotic; Cardiotonic Agents; Cholinergic Agonists; Miotics; Muscarinic Agonists; Nicotinic Agonists; Parasympathomimetics
Acetylcholine, 1%, or carbachol, 0.01%, is used in cataract extractions and certain other surgical procedures on the anterior segment when it is desired to produce miosis rapidly; the action of acetylcholine is brief. For the chronic therapy of noncongestive, wide-angle glaucoma, carbachol (0.75 to 3.0%) has been employed.
Carbachol has been used in the treatment of postoperative intestinal atony and postoperative retention of urine, for which it has been given by subcutaneous injection ... or by mouth. It has also been used to stop supraventricular paroxysmal tachycardia when all other measures have failed. Carbachol has a miotic action and eye-drops ... have been used to lower intraocular pressure in glaucoma ... Even in comparatively late cases of sun blindness the symptoms could in many instances be alleviated ... by retrobulbar injection of carbachol.
Pilocarpine (or occasionally carbachol) is used to lower intraocular pressure in the emergency treatment of acute (congestive) angle-closure glaucoma prior to surgery.
For more Therapeutic Uses (Complete) data for CARBACHOL CHLORIDE (11 total), please visit the HSDB record page.

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Drug Warnings
Topical carbachol shares the toxic potentials of the direct-acting miotics, and the usual precautions of miotic therapy should be observed. The manufacturer states that intraocular carbachol does not produce the adverse effects of topically applied carbachol; bullous keratopathy and postoperative iritis following cataract extraction have been reported in some patients.
Corneal edema may occur if excessive amounts of carbachol are introduced into the anterior chamber or if the drug is used in patients with an already compromised endothelium, eg, Fuchs' dystrophy, corneal transplants, cataract surgery that requires more manipulation than usual.
It is recommended that carbachol should not be used as eye-drops in patients with a corneal abrasion as there may be excessive absorption. The sensitivity of asthmatic patients to carbachol bronchoconstriction was increased when inhalation of carbachol was preceded by maximum respiratory maneurvers.
Drugs of this class should be admin only by the oral or subcutaneous route for systemic effects; they are also used locally in the eye. If they are given intravenously or intramuscularly, their relative selectivity of action no longer holds, and the incidence and severity of toxic side effects are greatly increased. /Choline esters/
For more Drug Warnings (Complete) data for CARBACHOL CHLORIDE (10 total), please visit the HSDB record page.

C6H15CLN2O2

182.65

182.082

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

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, 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.)