Карбахол

Описание

Unlike acetylcholine and methacholine, carbachol contains a carbamino functional group instead of an acetyl group, which is not responsive to hydrolysis by cholinesterase. In vitro studies have shown that the rate of hydrolysis is at least twice as slow as that of acetylcholine.

Химические свойства

Carbachol chloride is a crystalline odorless powder which, on standing in an open container, develops a faint odor resembling that of an aliphatic amine.

Использование

Carbachol is a powerful cholinic ester that stimulates both muscarinic and nicotinic receptors, as well as exhibits all of the pharmacological properties of acetylcholine while in addition resulting in vasodilation, a decrease in heart rate, an increase in tone and contractability of smooth muscle, stimulation of salivary, ocular, and sweat glands as well as autonomic ganglia and skeletal muscle. For this reason, use of carbachol, like acetylcholine, is limited. The exception is that it is used in ophthalmological practice and postoperational intestines and bladder atony. Upon administration in the eye, the pupil constricts and the intraocular pressure is reduced. It is used for severe chronic glaucoma.

Использование

Carbachol is a cholinergic agonist and is used for the treatment of glaucoma. It is also used as ophthalmic solution (eye drops) during ophthalmic surgery.

Определение

An acetylcholine counterfit molecule that is not inactivated by acetylcholinesterase and is a slowly hydrolyzed cholinergic agonist that acts at both muscarinic and nicotinic receptors.

Общее описание

Carbachol forms a carbamylester in the active site of AChE, which is hydrolyzedmore slowly than an acetyl ester. This slower hydrolysis ratereduces the amount of free enzyme and prolongs the durationof ACh in the synapse. Carbachol also stimulates theautonomic ganglia and causes contraction of skeletal musclebut differs from a true muscarinic agent in that it does nothave cardiovascular activity despite the fact that it seems toaffect M2 receptors.

Реакции воздуха и воды

Hygroscopic.

Профиль реактивности

Carbachol 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.

Опасность

Deadly poison; may cause lowered blood pressure, venous dilation, nausea or vomiting, sweating and lachrymation; a parasympathetic nerve stimulant.

Угроза здоровью

Highly toxic by mouth.

Пожароопасность

When heated to decomposition, Carbachol emits very toxic fumes of chloride and nitrogen oxides. The aqueous solution is stable even when heated.

Биологическая активность

Cholinergic receptor agonist that is resistant to the action of cholinesterases. Blocks apoptosis in cerebellar granule neurons.

Клиническое использование

Carbachol is a miotic and has been used to reduce the intraoculartension of glaucoma when a response cannot beobtained with pilocarpine or neostigmine. Penetration of thecornea is poor but can be enhanced by the use of a wettingagent in the ophthalmic solution. In addition to its topicaluse for glaucoma, carbachol is used during ocular surgery,when a more prolonged miosis is required than can be obtainedwith ACh chloride.

Синтез

Carbachol, 2-carbamoyloxy-N,N,N-trimethylethyl ammonium chloride (13.1.7), is made by reacting 2-chloroethanol with phosgene, which forms 2-chloroethyl chloroformate (13.1.5). Upon reaction with ammonia, it turns into the corresponding amide (13.1.6), which is further reacted with an equimolar quantity of trimethylamine, giving carbachol (13.1.7) [9¨C13].

Возможный контакт

Used in veterinary medicine as a cholinergic; parasympathomimetic, used chiefly in large animals, especially for colic in the horse

Перевозки

UN3249 Medicine, solid, toxic, n.o.s., Hazard Class: 6.1; Labels: 6.1-Poisonous materials. UN2811 Toxic solids, organic, n.o.s., Hazard Class: 6.1; Labels: 6.1- Poisonous materials, Technical Name Required.

Несовместимости

Carbachol chloride is a carbamate ester. Esters are generally incompatible with nitrates. Moisture may cause hydrolysis or other forms of decomposition. Carbamates are incompatible with strong acids and bases, and especially incompatible with strong reducing agents such as hydrideds and active metals. Contact with active metals or nitrides form flammable gaseous hydrogen. Incompatible with strongly oxidizing acids, peroxides, and hydroperoxides.

Утилизация отходов

It is inappropriate and possibly dangerous to the environment to dispose of expired or waste pharmaceuticals by flushing them down the toilet or discarding them to the trash. Household quantities of expired or waste pharmaceuticals may be mixed with wet cat litter or coffee grounds, double-bagged in plastic, discard in trash. Larger quantities shall carefully take into consideration applicable DEA, EPA, and FDA regulations. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged, and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.