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3D model (JSmol) | |
| ChemSpider | |
PubChem CID | |
CompTox Dashboard (EPA) | |
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| Properties | |
| C6H14ClNO | |
| Molar mass | 151.63 g·mol−1 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). | |
Ethylcholine mustard is a neurotoxic nitrogen mustard that destroys cholinergic neurons. [2] [3] It's the hydrolysis product of the HN1 vesicant. [1]
Under aqueous condition, ethylcholine mustard forms the highly reactive ethylcholine aziridinium (AF64A) ion. AF64A is transported into cholinergic neurons by the choline transporter. AF64A irreversibly inhibits the choline acetyltransferase and thereby inhibits acetylcholine synthesis. AF64A can also produce cytotoxic effects, leading to cell death. [2] [3]
The aziridinium ion can be isolated as picrylsulfonate salt. [1]
Acetylcholine (ACh) is an organic compound 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.
Choline is a cation with the chemical formula [(CH3)3NCH2CH2OH]+. Choline forms various salts, for example choline chloride and choline bitartrate.
Cholinergic agents are compounds which mimic the action of acetylcholine and/or butyrylcholine. In general, the word "choline" describes the various quaternary ammonium salts containing the N,N,N-trimethylethanolammonium cation. Found in most animal tissues, choline is a primary component of the neurotransmitter acetylcholine and functions with inositol as a basic constituent of lecithin. Choline also prevents fat deposits in the liver and facilitates the movement of fats into cells.
Choline acetyltransferase is a transferase enzyme responsible for the synthesis of the neurotransmitter acetylcholine. ChAT catalyzes the transfer of an acetyl group from the coenzyme acetyl-CoA to choline, yielding acetylcholine (ACh). ChAT is found in high concentration in cholinergic neurons, both in the central nervous system (CNS) and peripheral nervous system (PNS). As with most nerve terminal proteins, ChAT is produced in the body of the neuron and is transported to the nerve terminal, where its concentration is highest. Presence of ChAT in a nerve cell classifies this cell as a "cholinergic" neuron. In humans, the choline acetyltransferase enzyme is encoded by the CHAT gene.
A parasympathomimetic drug, sometimes called a cholinomimetic drug or cholinergic receptor stimulating agent, is a substance that stimulates the parasympathetic nervous system (PSNS). These chemicals are also called cholinergic drugs because acetylcholine (ACh) is the neurotransmitter used by the PSNS. Chemicals in this family can act either directly by stimulating the nicotinic or muscarinic receptors, or indirectly by inhibiting cholinesterase, promoting acetylcholine release, or other mechanisms. Common uses of parasympathomimetics include glaucoma, Sjögren syndrome and underactive bladder.
Coluracetam is a purported nootropic agent of the racetam family. It is contains a chemical group that is a bioisostere of the 9-amino-tetrahydroacridine family. It was initially developed and tested by the Mitsubishi Tanabe Pharma Corporation for Alzheimer's disease. After the drug failed to reach endpoints in its clinical trials it was in-licensed by BrainCells Inc for investigations into major depressive disorder (MDD), which was preceded by being awarded a "Qualifying Therapeutic Discovery Program Grant" by the state of California. Findings from phase IIa clinical trials have suggested that it would be a potential medication for comorbid MDD with generalized anxiety disorder (GAD). BrainCells Inc is currently out-licensing the drug for this purpose. It may also have potential use in prevention and treatment of ischemic retinopathy and retinal and optic nerve injury.
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.
Nitrogen mustards (NMs) are cytotoxic organic compounds with the bis(2-chloroethyl)amino ((ClC2H4)2NR) functional group. Although originally produced as chemical warfare agents, they were the first chemotherapeutic agents for treatment of cancer. Nitrogen mustards are nonspecific DNA alkylating agents.
Neuromodulation is the physiological process by which a given neuron uses one or more chemicals to regulate diverse populations of neurons. Neuromodulators typically bind to metabotropic, G-protein coupled receptors (GPCRs) to initiate a second messenger signaling cascade that induces a broad, long-lasting signal. This modulation can last for hundreds of milliseconds to several minutes. Some of the effects of neuromodulators include: altering intrinsic firing activity, increasing or decreasing voltage-dependent currents, altering synaptic efficacy, increasing bursting activity and reconfigurating synaptic connectivity.
Hemicholinium-3 (HC3), also known as hemicholine, is a drug which blocks the reuptake of choline by the high-affinity choline transporter at the presynapse. The reuptake of choline is the rate-limiting step in the synthesis of acetylcholine; hence, hemicholinium-3 decreases the synthesis of acetylcholine. It is therefore classified as an indirect acetylcholine antagonist.
Bis(2-chloroethyl)ethylamine is the organic compound with the formula C2H5N(CH2CH2Cl)2. Often abbreviated HN1, it is a powerful vesicant and a nitrogen mustard gas used for chemical warfare. HN1 was developed in the 1920s and 1930s to remove warts and later as a military agent. Because of the latter use, it is a Schedule 1 chemical within the Chemical Weapons Convention and therefore use and production is strongly restricted. It has never been used in warfare.
The Vesicular acetylcholine transporter (VAChT) is a neurotransmitter transporter which is responsible for loading acetylcholine (ACh) into secretory organelles in neurons making acetylcholine available for secretion. It is encoded by Solute carrier family 18, member 3 (SLC18A3) gene, located within the first intron of the choline acetyltransferase gene. VAChT is able to transport ACh into vesicles by relying on an exchange between protons (H+) that were previously pumped into the vesicle diffusing out, thus acting as an antiporter. ACh molecules are then carried into the vesicle by the action of exiting protons. Acetylcholine transport utilizes a proton gradient established by a vacuolar ATPase.
Acetylcholinesterase (HGNC symbol ACHE; EC 3.1.1.7; systematic name acetylcholine acetylhydrolase), also known as AChE, AChase or acetylhydrolase, is the primary cholinesterase in the body. It is an enzyme that catalyzes the breakdown of acetylcholine and some other choline esters that function as neurotransmitters:
Bifemelane (INN) (Alnert, Celeport), or bifemelane hydrochloride (JAN), also known as 4-(O-benzylphenoxy)-N-methylbutylamine, is an antidepressant and cerebral activator that is widely used in the treatment of cerebral infarction patients with depressive symptoms in Japan, and in the treatment of senile dementia as well. It also appears to be useful in the treatment of glaucoma. Bifemelane acts as a monoamine oxidase inhibitor (MAOI) of both isoenzymes, with competitive (reversible) inhibition of MAO-A (Ki = 4.20 μM) (making it a reversible inhibitor of monoamine oxidase A (RIMA)) and non-competitive (irreversible) inhibition of MAO-B (Ki = 46.0 μM), and also acts (weakly) as a norepinephrine reuptake inhibitor. The drug has nootropic, neuroprotective, and antidepressant-like effects in animal models, and appears to enhance the cholinergic system in the brain.
Naphthylvinylpyridine (NVP) is a naphthalene derivative that possesses anticholinergic activity similar to that of atropine. However, NVP's method of acetylcholine (ACh) antagonism involves inhibiting the enzyme choline acetyltransferase.
The high-affinity choline transporter (ChT) also known as solute carrier family 5 member 7 is a protein in humans that is encoded by the SLC5A7 gene. It is a cell membrane transporter and carries choline into acetylcholine-synthesizing neurons.
Chlornaphazine, a derivative of 2-naphthylamine, is a nitrogen mustard that was developed in the 1950s for the treatment of polycythemia and Hodgkin's disease. However, a high incidence of bladder cancers in patients receiving treatment with chlornaphthazine led to use of the drug being discontinued.
A cholinergic neuron is a nerve cell which mainly uses the neurotransmitter acetylcholine (ACh) to send its messages. Many neurological systems are cholinergic. Cholinergic neurons provide the primary source of acetylcholine to the cerebral cortex, and promote cortical activation during both wakefulness and rapid eye movement sleep. The cholinergic system of neurons has been a main focus of research in aging and neural degradation, specifically as it relates to Alzheimer's disease. The dysfunction and loss of basal forebrain cholinergic neurons and their cortical projections are among the earliest pathological events in Alzheimer's disease.
N,N-Dimethyl-2-chloro-2-phenylethylamine(DMEA) is chemical compound that irreversibly inhibits the acetylcholinesterase. DMEA can cause intoxication in cats, resulting from respiratory failure to death, and progressive damage to the central nervous system in rats. Synthesis of DMEA can be obtained by treating N,N-dimethyl-2-hydroxy-2-phenylethylamine with thionyl chloride (SOCl2). This compound, when dissolved water, decomposes into a highly reactive aziridinium ion, N,N-dimethyl-2-phenylaziridinium (DPA). DPA binds to the anionic site of acetylcholinesterase, where it alkylates and irreversibly inhibits the enzyme. DMEA was also compared to N, N-dimethyl, 2-chloro-2-phenyl-1-methylethyl-amine (M-DMEA) and the results show that there is a difference between the degree of adrenergic blocking activity and their immonium ring stability in vitro.
Aziridiniums are the ionic form of the class of molecules known as aziridines.
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