2-((Aminocarbonyl)oxy)-N,N,N-tri-methylethan-aminiumchlorid

Hard prismatic crystals

White or faintly yellow crystals or crystalline powder

1 g in 1 ml water

1 g in 50 ml alcohol

Very slightly sol in dehydrated alcohol, more readily sol on boiling

1 g in 10 ml methanol

Practically insol in chloroform, ether, acetone

Breast Feeding; Lactation; Miotics; Muscarinic Agonists; Parasympathomimetics

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Ophthalmological preparations > Miotics and antiglaucoma medicines

392 to 401 °F (EPA, 1998)

200-203 °C, some decomposition

Hygroscopic

Ophthalmic soln of carbachol has a pH of 5-7; the commercially available intraocular injection has a pH of 6.5-7.5 /Soln/

Chlorocresol (0.025 to 0.1%) and chlorbutol (0.5%) were incompatible with a soln of carbachol (0.8%) and sodium chloride (0.69%), very slight precipitates forming on heating and increasing on standing. /Soln/

Incompatible with alkalies, iodine, and silver salts

Danger

H300 (100%): Fatal if swallowed [Danger Acute toxicity, oral]

P264, P270, P301+P316, P321, P330, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 72 reports by companies from 2 notifications to the ECHA C&L Inventory.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed drug products, incl carbachol, approved on the basis of safety and effectiveness by FDA under sections 505 and 507 of the Federal Food, Drug, and Cosmetic Act. /From Appendix A, Product Name Index/

CARBACHOL CHLORIDE is a carbamate ester. Carbamates are chemically similar to, but more reactive than amides. Like amides they form polymers such as polyurethane resins. Carbamates are incompatible with strong acids and bases, and especially incompatible with strong reducing agents such as hydrides. Flammable gaseous hydrogen is produced by the combination of active metals or nitrides with carbamates. Strongly oxidizing acids, peroxides, and hydroperoxides are incompatible with carbamates.

Releases of CERCLA hazardous substances are subject to the release reporting requirement of CERCLA section 103, codified at 40 CFR part 302, in addition to the requirements of 40 CFR part 355. Carbachol chloride is an extremely hazardous substance (EHS) subject to reporting requirements when stored in amounts in excess of its threshold planning quantity (TPQ) of 500/10,000 lbs.

Store in airtight containers. Protect from light.

Aqueous solutions are most stable to autoclaving when buffered to pH 3.5. Up to 5% decomposition may occur when unbuffered solutions are heated in an autoclave, and the decomposition increases the pH of the solutions; such autoclaved solutions should not be stored for more than a yr.

1.4 [mg/m3]

15 [mg/m3]

90 [mg/m3]

For emergency situations, wear a positive pressure, pressure-demand, full facepiece self-contained breathing apparatus (SCBA) or pressure- demand supplied air respirator with escape SCBA and a fully-encapsulating, chemical resistant suit. (EPA, 1998)

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 ... .

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

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

A report of life-threatening attacks of profuse sweating, intestinal cramps ... defecation, hypothermia, hypotension, and bradycardia in a 36-yr-old man due to carbachol intoxication /was recorded/. A 10-yr-old boy had died following similar attacks associated with repeated carbachol ingestion.

The most common ... effects of miotic therapy are painful ciliary or accommodative spasm, blurred vision or myopia, and poor vision in dim light. ... Other adverse effects ... include ciliary or conjunctival congestion, lacrimal passage stenosis, twitching of the eyelids, stinging, burning, lacrimation, ocular or brow pain, headache, photophobia ... /Miotics/

Tests of 0.01% solution introduced into the anterior chamber of eyes of human beings ... have shown no significant irritating or injurious action, but prompt miotic effect.

Carbachol, in doses sufficient to cause purgation /in animals/, produces a profound drop in the diastolic blood pressure. Larger doses aggravate this by inhibiting the heart itself.

All parasympathomimetic drugs, in toxic doses, stimulate all the secretions and produce severe gastrointestinal colic and diarrhea and dyspnea; the iris is markedly constricted; the heart rate is first increased and then slowed. Death may be due to respiratory paralysis or heart block. /Parasympathomimetic drugs/

The phenomenon of sudden mortality in the chick embryo, induced by the exogenous neurotransmitter /such as/ carbachol, is described. When introduced singly into eggs (albumen) in doses of 0.1 mg/egg, /the cmpd/ induced highly significant, sharply incr mortality (60-100%) when the introduction was on embryonic (incubation) days 8 to 12, but none if introduction was earlier. These ages follow the appearance of functional receptors (or receptor-effectors) for the substance. ... The involvement of receptors here have not been proved. Solvent alone (Ringer's solution for chick) had no effect, indicating that the procedures used were in themselves not lethal. ...

Tests of 0.01% solution intrduced into the anterior chamber of eyes of rabbits, cats ... have shown no significant irritating or injurious action, but prompt miotic effect.

LD50 Mouse oral 5 mg/kg

LD50 Mouse iv 0.3 mg/kg

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed drug products, incl carbachol, approved on the basis of safety and effectiveness by FDA under sections 505 and 507 of the Federal Food, Drug, and Cosmetic Act. /From Appendix A, Product Name Index/

Releases of CERCLA hazardous substances are subject to the release reporting requirement of CERCLA section 103, codified at 40 CFR part 302, in addition to the requirements of 40 CFR part 355. Carbachol chloride is an extremely hazardous substance (EHS) subject to reporting requirements when stored in amounts in excess of its threshold planning quantity (TPQ) of 500/10,000 lbs.

N07AB01

N - Nervous system

S - Sensory organs

QA - Alimentary tract and metabolism

QS - Sensory organs

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.

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.

CARBACHOL

Cholinergic Receptor Agonist [EPC]; Cholinergic Agonists [MoA]

Agents that have a strengthening effect on the heart or that can increase cardiac output. They may be CARDIAC GLYCOSIDES; SYMPATHOMIMETICS; or other drugs. They are used after MYOCARDIAL INFARCT; CARDIAC SURGICAL PROCEDURES; in SHOCK; or in congestive heart failure (HEART FAILURE).

Agents causing contraction of the pupil of the eye. Some sources use the term miotics only for the parasympathomimetics but any drug used to induce miosis is included here.

Drugs that bind to and activate cholinergic receptors.

A subclass of analgesic agents that typically do not bind to OPIOID RECEPTORS and are not addictive. Many non-narcotic analgesics are offered as NONPRESCRIPTION DRUGS.

MEDICATION (VET)

MEDICATION

Commercially available ophthalmic solutions contain benzalkonium chloride as preservative and wetting agent. ... Preparations: Ophthalmic - Injection, for intraocular use only 100 ug/ml (0.01%) Miostat Intraocular. Solution: 0.75%, Isopto Carbachol (with benzalkonium chloride; viscous); 1.5%, Isopto Carbachol (with benzalkonium chloride; viscous); 2.25%, Isopto (with benzalkonium chloride: viscous); 3% Isotop Carbachol (with benzalkomum chloride; viscous).

Eyedrops: APF has carbachol 750 mg, sodium chloride 700 mg, benzalkonium chloride soln 0.02 ml, disodium edetate 50 mg. Water for injections to 100 ml ... Another formula: carbachol 800 mg, anhydrous dextrose 5 g, chlorhexidine acetate 5 mg. Water for injection to 100 ml ...

Carbachol intraocular soln is a sterile soln of carbachol in an aqueous medium. It contains not less than 90.0% & not more than 115.0% of the labeled amt of Carbachol. It contains no preservatives or antimicrobial agents.