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| Formula | C8H20NO |
| Molar mass | 146.254 g·mol−1 |
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Triethylcholine is a drug which mimics choline, and causes failure of cholinergic transmission by interfering with synthesis of acetylcholine in nerve endings. [1]
Triethylcholine produces a slowly developing neuromuscular weakness that is exacerbated by exercise, resembling the symptoms of myasthenia gravis. It also has ganglionic blocking effects, causing transient autonomic symptoms such as hypotension. Muscles stimulated at a high contraction rate are much more affected than those stimulated at a low rate. The muscle weakness typically lasts for 80 to 120 minutes; it is partially relieved by rest. High doses may result in death from respiratory failure, particularly after exercise. Triethylcholine seems to interfere with the synthesis of acetylcholine in the presynaptic nerve endings, since its effects are reversed by choline but not by acetylcholinesterase inhibitors. However the mechanism of action is not definitely known. Animal experiments revealed a relatively low acute toxicity: intravenous administration of 10–25 mg/kg triethylcholine iodide produced slight to moderate exercise intolerance, while 100 mg/kg caused death in rabbits after continuous exercise. However, there was no full paralysis even at fatal doses. [2]
Lambert–Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder characterized by muscle weakness of the limbs.
Myasthenia gravis (MG) is a long-term neuromuscular junction disease that leads to varying degrees of skeletal muscle weakness. The most commonly affected muscles are those of the eyes, face, and swallowing. It can result in double vision, drooping eyelids, trouble talking, and trouble walking. Onset can be sudden. Those affected often have a large thymus or develop a thymoma.
Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Parts in the body that use or are affected by acetylcholine are referred to as cholinergic. Substances that increase or decrease the overall activity of the cholinergic system are called cholinergics and anticholinergics, respectively.
Weakness is a symptom of a number of different conditions. The causes are many and can be divided into conditions that have true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, including muscular dystrophy and inflammatory myopathy. It occurs in neuromuscular junction disorders, such as myasthenia gravis.
The enzyme cholinesterase (EC 3.1.1.8, choline esterase; systematic name acylcholine acylhydrolase) catalyses the hydrolysis of choline-based esters:
A neuromuscular junction is a chemical synapse between a motor neuron and a muscle fiber.
Physostigmine is a highly toxic parasympathomimetic alkaloid, specifically, a reversible cholinesterase inhibitor. It occurs naturally in the Calabar bean and the fruit of the Manchineel tree.
End plate potentials (EPPs) are the voltages which cause depolarization of skeletal muscle fibers caused by neurotransmitters binding to the postsynaptic membrane in the neuromuscular junction. They are called "end plates" because the postsynaptic terminals of muscle fibers have a large, saucer-like appearance. When an action potential reaches the axon terminal of a motor neuron, vesicles carrying neurotransmitters are exocytosed and the contents are released into the neuromuscular junction. These neurotransmitters bind to receptors on the postsynaptic membrane and lead to its depolarization. In the absence of an action potential, acetylcholine vesicles spontaneously leak into the neuromuscular junction and cause very small depolarizations in the postsynaptic membrane. This small response (~0.4mV) is called a miniature end plate potential (MEPP) and is generated by one acetylcholine-containing vesicle. It represents the smallest possible depolarization which can be induced in a muscle.
Tubocurarine is a toxic alkaloid historically known for its use as an arrow poison. In the mid-1900s, it was used in conjunction with an anesthetic to provide skeletal muscle relaxation during surgery or mechanical ventilation. It is now rarely used as an adjunct for clinical anesthesia because safer alternatives, such as cisatracurium and rocuronium, are available.
Neuromuscular-blocking drugs block neuromuscular transmission at the neuromuscular junction, causing paralysis of the affected skeletal muscles. This is accomplished via their action on the post-synaptic acetylcholine (Nm) receptors.
Ocular myasthenia gravis (MG) is a disease of the neuromuscular junction resulting in hallmark variability in muscle weakness and fatigability. MG is an autoimmune disease where anomalous antibodies are produced against the naturally occurring acetylcholine receptors in voluntary muscles. MG may be limited to the muscles of the eye, leading to abrupt onset of weakness/fatigability of the eyelids or eye movement. MG may also involve other muscle groups.
A cholinergic crisis is an over-stimulation at a neuromuscular junction due to an excess of acetylcholine (ACh), as a result of the inactivity of the AChE enzyme, which normally breaks down acetylcholine.
Gallamine triethiodide (Flaxedil) is a non-depolarising muscle relaxant. It acts by combining with the cholinergic receptor sites in muscle and competitively blocking the transmitter action of acetylcholine. Gallamine is a non-depolarising type of blocker as it binds to the acetylcholine receptor but does not have the biological activity of acetyl choline. Gallamine triethiodide has a parasympatholytic effect on the cardiac vagus nerve, which causes tachycardia and occasionally hypertension. Very high doses cause histamine release.
Methyllycaconitine (MLA) is a diterpenoid alkaloid found in many species of Delphinium (larkspurs). In common with many other diterpenoid alkaloids, it is toxic to animals, although the acute toxicity varies with species. Early research was focused on identifying, and characterizing the properties of methyllycaconitine as one of the principal toxins in larkspurs responsible for livestock poisoning in the mountain rangelands of North America. Methyllycaconitine has been explored as a possible therapeutic agent for the treatment of spastic paralyses in man, and it has been shown to have insecticidal properties. Most recently, it has become an important molecular probe for studying the pharmacology of the nicotinic acetylcholine receptor.
Thyrotoxic myopathy (TM) is a neuromuscular disorder that develops due to the overproduction of the thyroid hormone thyroxine. Also known as hyperthyroid myopathy, TM is one of many myopathies that lead to muscle weakness and muscle tissue breakdown. Evidence indicates the onset may be caused by hyperthyroidism. There are two known causes of hyperthyroidism that lead to development thyrotoxic myopathy including a multinodular goiter and Graves' disease. Physical symptoms of TM may include muscle weakness, the breakdown of muscle tissue, fatigue, and heat intolerance. Physical acts such as lifting objects and climbing stairs may become increasingly difficult. If untreated, TM can be an extremely debilitating disorder that can, in extreme rare cases, lead to death. If diagnosed and treated properly the effects can be controlled and in most cases reversed leaving no lasting effects.
Neuromuscular junction disease is a medical condition where the normal conduction through the neuromuscular junction fails to function correctly.
Chlorethoxyfos is an organophosphate acetylcholinesterase inhibitor used as an insecticide. It is registered for the control of corn rootworms, wireworms, cutworms, seed corn maggot, white grubs and symphylans on corn. The insecticide is sold under the trade name Fortress by E.I. du Pont de Nemours & Company.
Candicine is a naturally occurring organic compound that is a quaternary ammonium salt with a phenethylamine skeleton. It is the N,N,N-trimethyl derivative of the well-known biogenic amine tyramine, and, being a natural product with a positively charged nitrogen atom in its molecular structure, it is classed as an alkaloid. Although it is found in a variety of plants, including barley, its properties have not been extensively studied with modern techniques. Candicine is toxic after parenteral administration, producing symptoms of neuromuscular blockade; further details are given in the "Pharmacology" section below.
Autonomic drugs can either inhibit or enhance the functions of the parasympathetic and sympathetic nervous systems. This type of drug can be used to treat a wide range of diseases, such as glaucoma, asthma, urinary, gastrointestinal and cardiopulmonary disorders.
Neuromuscular blocking agents, or in abbreviation, NMBAs, are chemical agents that paralyse skeletal muscles by blocking the movement of neurotransmitter at the neuromuscular junction. They are often used during general anesthesia to optimize intubating and surgical conditions, specifically to facilitate endotracheal intubation. This class of medications helps to reduce patient movement, breathing, or ventilator dyssynchrony and allows lower insufflation pressures during laparoscopy including the generation of nerve impulses. It has several indications for use in the intense care unit. It can help reduce hoarseness in voice as well as injury to the vocal cord during intubation. In addition, it plays an important role in facilitating mechanical ventilation in patients with poor lung function. In the following section, neuromuscular blocking agent's history, usages, mechanisms, side effects, interactions and pharmacology will further be elaborated and discussed.
