Edrophonium

Edrophonium
Clinical data
Trade names	Tensilon
AHFS/Drugs.com	FDA Professional Drug Information
ATC code	V04CX07 ( WHO );
Identifiers
	IUPAC name N-Ethyl-3-hydroxy-N,N-dimethylbenzenaminium;
CAS Number	312-48-1 ;
PubChem CID	8307 ;
DrugBank	DB01010 ;
ChemSpider	8006 ;
UNII	70FP3JLY7N ;
KEGG	D00994 ;
ChEBI	CHEBI:4759 ;
ChEMBL	ChEMBL1128 ;
CompTox Dashboard (EPA)	DTXSID4046943 ;
Chemical and physical data
Formula	C10H16NO+
Molar mass	166.244 g·mol−1
3D model (JSmol)	Interactive image ;
	SMILES [Cl-].Oc1cccc(c1)[N+](C)(CC)C;
	InChI InChI=1S/C10H15NO.ClH/c1-4-11(2,3)9-6-5-7-10(12)8-9;/h5-8H,4H2,1-3H3;1H ; Key:BXKDSDJJOVIHMX-UHFFFAOYSA-N ;
	(what is this?) (verify)

Last updated December 19, 2021

Edrophonium is a readily reversible acetylcholinesterase inhibitor. It prevents breakdown of the neurotransmitter acetylcholine and acts by competitively inhibiting the enzyme acetylcholinesterase, mainly at the neuromuscular junction. It is sold under the trade names Tensilon and Enlon (according to FDA Orange Book).

Clinical uses

Edrophonium (by the so-called Tensilon test) is used to differentiate myasthenia gravis from cholinergic crisis and Lambert-Eaton. In myasthenia gravis, the body produces autoantibodies which block, inhibit or destroy nicotinic acetylcholine receptors in the neuromuscular junction. Edrophonium—an effective acetylcholinesterase inhibitor—will reduce the muscle weakness by blocking the enzymatic effect of acetylcholinesterase enzymes, prolonging the presence of acetylcholine in the synaptic cleft. It binds to a Serine-103 allosteric site, while pyridostigmine and neostigmine bind to the AchE active site for their inhibitory effects. In a cholinergic crisis, where a person has too much neuromuscular stimulation, edrophonium will make the muscle weakness worse by inducing a depolarizing block. However, the edrophonium and ice pack tests are no longer recommended as first-line tests due to false positive results. In practice, the edrophonium test has been replaced by testing for autoantibodies, including acetylcholine receptor (AchR) autoantibodies and muscle specific tyrosine kinase (MuSK) autoantibodies.^[1]^[2]

Lambert-Eaton myasthenic syndrome (LEMS), is similar to myasthenia gravis in that it is an autoimmune disease. However, in LEMS the neuron is unable to release enough acetylcholine for normal muscle function due to autoantibodies attacking P/Q-type calcium channel that are necessary for acetylcholine release. This means there is insufficient calcium ion influx into presynaptic terminal resulting in reduced exocytosis of acetylcholine containing vesicles. Consequently, there will typically be not as much increase in muscle strength observed after edrophonium injection, if any with LEMS.

The Tensilon test may also be used to predict if neurotoxic paralysis caused by snake envenomation is presynaptic or postsynaptic. If it is a postsynaptic then paralysis will be temporally reversed, indicating that can be reversed by adequate antivenom therapy. If the neurotoxic is presynaptic then the Tensilon test will show no response and antivenom will not reverse such paralysis. In this instance reversal of paralysis will not occur until the damaged terminal axons at the neuromuscular junction have recovered, this may take days or weeks.^[3]

The drug may also be used for reversal of neuromuscular blockade at the end of a surgical procedure.^[4]

Chemistry

Edrophonium, ethyl-(3-hydroxyphenyl)dimethylammonium chloride, is made by reacting 3-dimethylaminophenol with ethyl bromide, which forms ethyl(3-hydroxyphenyl)dimethylammonium bromide, the bromine atom of which is replaced with a chlorine atom by reacting it with silver chloride, giving edrophonium.^[5]

Pharmacokinetics

The drug has a brief duration of action, about 10–30 mins.^[4]

Related Research Articles

Myasthenia gravis Autoimmune disease resulting in skeletal muscle weakness

Myasthenia gravis (MG) is a long-term neuromuscular 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 Organic chemical and neurotransmitter

Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals as a neurotransmitter—a chemical message released by nerve cells to send signals to other cells, such as neurons, muscle cells and gland cells. 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.

Acetylcholine receptor Integral membrane protein

An acetylcholine receptor is an integral membrane protein that responds to the binding of acetylcholine, a neurotransmitter.

In biochemistry, a cholinesterase or choline esterase is a family of esterases that lyses choline-based esters, several of which serve as neurotransmitters. Thus, it is either of two enzymes that catalyze the hydrolysis of these cholinergic neurotransmitters, such as breaking acetylcholine into choline and acetic acid. These reactions are necessary to allow a cholinergic neuron to return to its resting state after activation. For example, in muscle contraction, acetylcholine at a neuromuscular junction triggers a contraction; but for the muscle to relax afterward, rather than remaining locked in a tense state, the acetylcholine must be broken down by a choline esterase. The main type for that purpose is acetylcholinesterase ; it is found mainly in chemical synapses and red blood cell membranes. The other type is butyrylcholinesterase ; it is found mainly in the blood plasma.

A neuromuscular junction is a chemical synapse between a motor neuron and a muscle fiber.

Neostigmine is a medication used to treat myasthenia gravis, Ogilvie syndrome, and urinary retention without the presence of a blockage. It is also used in anaesthesia to end the effects of non-depolarising neuromuscular blocking medication. It is given by injection either into a vein, muscle, or under the skin. After injection effects are generally greatest within 30 minutes and last up to 4 hours.

Physostigmine is a highly toxic parasympathomimetic alkaloid, specifically, a reversible cholinesterase inhibitor. It occurs naturally in the Calabar bean and the Manchineel tree.

Pyridostigmine A medication for myasthenia gravis

Pyridostigmine is a medication used to treat myasthenia gravis and underactive bladder. It is also used together with atropine to end the effects of neuromuscular blocking medication of the non-depolarizing type. It is typically given by mouth but can also be used by injection. The effects generally begin within 45 minutes and last up to 6 hours.

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.

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.

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.

MuSK is a receptor tyrosine kinase required for the formation and maintenance of the neuromuscular junction. It is activated by a nerve-derived proteoglycan called agrin.

A tensilon test, also called a edrophonium test, is a pharmacological test used for the diagnosis of certain neural diseases, especially myasthenia gravis. It is also used to distinguish a myasthenic crisis from a cholinergic crisis in individuals undergoing treatment for myasthenia gravis.

Triethylcholine is a drug which mimics choline, and causes failure of cholinergic transmission by interfering with synthesis of acetylcholine in nerve endings.

Ambenonium is a cholinesterase inhibitor used in the management of myasthenia gravis.

Congenital myasthenic syndrome (CMS) is an inherited neuromuscular disorder caused by defects of several types at the neuromuscular junction. The effects of the disease are similar to Lambert-Eaton Syndrome and myasthenia gravis, the difference being that CMS is not an autoimmune disorder. There are only 600 known family cases of this disorder and it is estimated that the chance of having it is 1 in 200,000.

Acetylcholinesterase, also known as AChE or acetylhydrolase, is the primary cholinesterase in the body. It is an enzyme that catalyzes the breakdown of acetylcholine and of some other choline esters that function as neurotransmitters. AChE is found at mainly neuromuscular junctions and in chemical synapses of the cholinergic type, where its activity serves to terminate synaptic transmission. It belongs to carboxylesterase family of enzymes. It is the primary target of inhibition by organophosphorus compounds such as nerve agents and pesticides.

Neuromuscular junction disease is a medical condition where the normal conduction through the neuromuscular junction fails to function correctly.

Repetitive nerve stimulation is a variant of the nerve conduction study where electrical stimulation is delivered to a motor nerve repeatedly several times per second. By observing the change in the muscle electrical response (CMAP) after several stimulations, a physician can assess for the presence of a neuromuscular junction disease, and differentiate between presynaptic and postsynaptic conditions. The test was first described by German neurologist Friedrich Jolly in 1895, and is also known as Jolly's test.

EPN is an insecticide of the phosphonothioate class. It is used against pests such as European corn borer, rice stem borer, bollworm, tobacco budworm, and boll weevil.

References

↑ Meriggioli MN, Sanders DB (July 2012). "Muscle autoantibodies in myasthenia gravis: beyond diagnosis?". Expert Review of Clinical Immunology. 8 (5): 427–38. doi:10.1586/eci.12.34. PMC 3505488 . PMID 22882218.
↑ Caliandro P, Evoli A, Stålberg E, Granata G, Tonali P, Padua L (December 2009). "The difficulty in confirming clinical diagnosis of myasthenia gravis in a seronegative patient: a possible neurophysiological approach". Neuromuscular Disorders. 19 (12): 825–7. doi:10.1016/j.nmd.2009.09.005. PMID 19846306. S2CID 25219973.
↑ Cameron P, Jelinek G, Everitt I, Browne G, Raftos J (September 2011). Textbook of Paediatric Emergency (2nd ed.). Churchill Livingstone. pp. 443–4. ISBN 978-0-7020-5636-9.
1 2 Tripati KD (2004). Essentials of Medical Pharmacology (5th ed.). Jaypee Brothers Medical. p. 84. ISBN 978-81-8061-187-2.
↑ US 2647924,Aeschlimann JA, Stempel A,issued 1953