D-TUBOCURARINE CHLORIDE CAS 57-94-3

Introduction：Basic information about D-TUBOCURARINE CHLORIDE CAS 57-94-3, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

D-TUBOCURARINE CHLORIDE Basic information

• Product Name: D-TUBOCURARINE CHLORIDE
• Synonyms: (+)-tubocurarinehydrochloride;amerizol;d-tubocurarinehydrochloride;intocostrin;intocostrinet;tubadil;tubarine;tubocurarinehydrochloride
• CAS: 57-94-3
• MF: C37H41N2O6.ClH.Cl
• MW: 681.65
• EINECS: 200-356-9
• Product Categories: Acetylcholine receptor;Organics;AntagonistsIon Channels;Cholinergics;Ligand-Gated Ion Channels;Neurotransmitters;Nicotinic Acetylcholine Receptor Modulators;Nicotinic
• Mol File: 57-94-3.mol

D-TUBOCURARINE CHLORIDE Chemical Properties

• Melting point: 274～275℃
• alpha: D20-25 +215° (c = 0.25-0.3 g/100 ml)
• density: 1.2074 (rough estimate)
• refractive index: 1.7350 (estimate)
• storage temp.: 2-8°C
• solubility: Soluble to 25 mM in water and to 10 mM in DMSO
• pka: pK: 7.4(at 25℃)
• form: Powder
• color: white
• Water Solubility: Soluble to 25 mM in water
• InChIKey: GXFZCDMWGMFGFL-KKXMJGKMSA-N
• SMILES: [Cl-].[Cl-].[N+]1([C@@H]2Cc3cc(c(cc3)O)Oc4cc5c(cc4OC)CC[N+H]([C@H]5Cc6ccc(cc6)Oc7c2c(cc(c7O)OC)CC1)C)(C)C

Safety Information

• Hazard Codes: T
• Risk Statements: 25
• Safety Statements: 45
• RIDADR: UN 1544 6.1/PG 2
• WGK Germany: 3
• RTECS: YO4900000
• HazardClass: 6.1(b)
• PackingGroup: III
• Storage Class: 6.1A - Combustible, acute toxic Cat. 1 and 2 very toxic hazardous materials
• Hazard Classifications: Acute Tox. 2 Oral
• Toxicity: LD50 in mice, rats (mg/kg): 33.2, 27.8 orally in DMSO; 59.5, 36.9 orally in water (Rosen)

D-TUBOCURARINE CHLORIDE Usage And Synthesis

Description

The name curare is derived from the native Guyana MukusiIndian word wurari. In 1596, Sir Walter Raleigh referred tocurare in The Discovery of the Large, Rich, and Beautiful Empire ofGuiana. In 1780, Abbe Felix Fontana identified the action ofcurare on voluntary muscles. In 1800, Alexander von Humboldtdescribed the extraction of curare. In 1811, Sir BenjaminCollins Brodie determined that complete recovery from curarepoisoning is possible provided artificial ventilation is maintained.In 1825, Charles Waterton brought curarep to Europe,and in 1835 Sir Robert Hermann Schomburgk classified andnamed the vine Strychnos toxifera. In 1850, George Harleydemonstrated that curare could be used to treat tetanus andstrychnine poisoning. By 1868, Claude Bernard and AlfredVulpian had identified the site of action of curare as the motorend plate. From 1887, curare was marketed for medical use byBurroughs Welcome. In 1900, Jacob Pal recognized thatphysostigmine could be used to antagonize the effects ofcurare. In 1912, Arthur Lawen demonstrated the use of curareduring surgery, but this potential was not realized as the findingwas published in German. In 1914, Henry Hallett Dale described the action of acetylcholine. In 1935, Harold Kingisolated D-tubocurarine and described its structure, while in1936 Dale revealed the role of acetylcholine in neuromusculartransmission and the mechanism of action for curare. In 1940,Abram Elting Bennett revealed that curare could be used toreduce trauma during metrazol-induced convulsive therapy forspastic disorders in children. In 1942, Harold Griffith and EnidJohnson used curare to augment general anesthesia whenperforming an appendectomy. Curare was used surgically untilthe development of safer synthetic neuromuscular blockinganalogues such as Pancuronium (in 1964), Vecuronium(in 1979), Mivacurium (in 1993), and Rocuronium (in 1994).

Chemical Properties

White to light-tan crystalline alkaloid;odorless. Mp 270C with decomposition. Soluble inwater and alcohol; insoluble in acetone, chloroform,and ether; aqueous solution is strongly dextrorotatory(specific rotation for 1% solution of anhydrous?208 to +218 degrees).

Physical properties

Appearance: white or slightly yellow crystalline powder. Solubility: it can be dissolved 50?mg/ml (22?°C) in water; easily soluble in methanol and ethanol; insoluble in ether, pyridine, chloroform, benzene, and acetone; and dissolved in sodium hydroxide solution. Specific optical rotation: +210 to +224°. Melting point: anhydrous 274–275?°C (decomposition)

History

Tubocurarine is a kind of alkaloid isolated from various plant extract alkaloid arrow poisons originating from Central and South America, with a common name curare. The active dextrorotatory form was first purified by R.?Boehm in 1879. The drug was first used in clinical practice in 1942, and it was the first typical non-depolarizing muscle relaxant .
In the 1970s, Chinese scientists isolated the levo isomer of tubocurarine from Cyclea hainansis and Cyclea barbata Miers (Menispermaceae). Its diiodomethane salt showed better relaxation on striated muscle. Another derivative dimethyl-Lcurine dimethochloride further enhanced significantly the muscle relaxation efficacy
Cissampelosime methiodide is another kind of muscle relaxant independently developed in China, which is isolated from the Dai medicine Yahulu (Menispermaceae plant Cissampelos pareira). It was mainly formulated into injection and exhibited significant striate muscle relaxation as its Chinese name means . The discovery of Cissampelosime methiodide led into the innovative development of traditional Dai medicine which was later incorporated into the Pharmacopoeia of the People’s Republic of China (1977)

Uses

Neuromuscular blocking agent.

Uses

Historically, curare was first used as a paralyzing arrow/dartpoison by indigenous South Americans. Later, curare was usedas a muscle relaxant during surgery. Previously, to enable deepsurgery, increased relaxation could only be achieved by higherand hence riskier quantities of general anesthetic. Being able tocontrol the degree of muscle relaxation independently of thedepth of sedation greatly improves survival, although bringingan associated risk of awareness while anesthetized.

Hazard

Highly toxic.

Biological Activity

Competitive, non-selective nicotinic acetylcholine receptor antagonist; causes skeletal muscle relaxation. Also a 5-HT 3 and GABA A receptor antagonist.

Pharmacology

The dextroisomer of tubocurarine has pharmacological activity. It is classified into a non-depolarizing muscle relaxant and also known as competitive muscular relaxant. It binds the N2 cholinergic receptor on the motor nerve endplate and competitively blocks ACh-mediated depolarization, thus relaxing skeletal muscle.
The drug is difficult to absorb under oral administration. For the intravenous injection, onset time is 4–6?min. Upon administration of the drug, muscles used in rapid exercise such as eye muscle first relax, and then the muscles in the limbs, neck, and trunk relax too, followed by intercostal muscle relaxation and abdominal breathing. If the dose is increased, it can ultimately cause diaphragmatic paralysis until the breathing stops. The order of muscle relaxation recovery is contrary to that of muscle relaxation, i.e., the diaphragm is the fastest recovered. This drug is clinically used for anesthesia and adjuvant drugs such as tracheal intubation and thoracoabdominal surgery
This drug also blocks ganglion and the release of histamine, causing a decline in heart rate and blood pressure, bronchial spasm, increased saliva secretion, etc. Artificial respiration and the use of neostigmine are needed when large doses cause respiratory muscle paralysis. Contraindications are myasthenia gravis, bronchial asthma, and severe shock.

Clinical Use

The drug known for the muscle relaxants is mainly used for abdominal surgery and was once used for the treatment of tremor paralysis, tetanus, rabies, poison, and so on. For adults, the amount of one intravenous injection is 6–9?mg and can increase to 3–4.5?mg if necessary (the amount should be reduced to 1/3?in ether anesthesia). The action lasts for 20–40? min. The injection can be repeated according to the length of the operation time and muscle relaxation needs, and the dose is half of the first. For electrical shock, a dose of 0.165?mg/kg every time was administrated in 30–90?s. For diagnosis of myasthenia gravis, a dose of 0.004–0.033?mg/kg everytime was used. However, attention must be paid that the drug can lead to the risk of paralysis of the respiratory muscles; emergency medicine and equipment must be prepared before. Oxygen supply, endotracheal intubation, and artificial respiration or injection of neostigmine at the same time (or phenolic ammonium chloride) can be carried out to counteract breathing stopping. It is contraindicated for the patients with myasthenia gravis. In addition, depolarizing muscle relaxants such as succinylcholine antagonizes non-depolarized muscle relaxant tubocurarine, and the clinical combination should be avoided.

Safety Profile

Poison by ingestion,intravenous, intraperitoneal, andsubcutaneous routes. Human toxicity: Largedoses and overdoses may cause respiratoryparalysis and hypotension. When heated todecomposition it emits very toxic fumes ofNOx and Cl-. Used as a muscle relaxant.

Environmental Fate

D-Tubocurarine acts as a non-depolarizing competitive antagonistat nicotinic acetylcholine receptors on the motor endplate of the neuromuscular junction, causing the relaxation ofskeletal muscle. D-Tubocurarine competes with at least an equalaffinity to acetylcholine, and at the same position on nicotinicreceptors. Hence curare does not affect cardiac muscle, smoothmuscle, or glandular secretions. Flaccid paralysis begins withina minute and progressively prevents movement of the eyes,limbs, and finally trunk. Death due to respiratory paralysis canoccur within 3–20 min.

storage

Store at +4°C

Purification Methods

Crystallise this chloride from water. It forms various hydrates. The hydrochloride pentahydrate has m 268-269o (from H2O) and [] D +190o (0.5, H2O). Its solubility in H2O at 25o is 50mg/mL. [Beilstein 27 II 897, 27 III/IV 8727.]