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

form 

Powder

pka

pK: 7.4(at 25℃)

Water Solubility 

Soluble to 25 mM in water

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

Toxicity

LD50 in mice, rats (mg/kg): 33.2, 27.8 orally in DMSO; 59.5, 36.9 orally in water (Rosen)

MSDS

• Language:English Provider:SigmaAldrich

D-TUBOCURARINE CHLORIDE Usage And Synthesis

Description

The name curare is derived from the native Guyana Mukusi Indian word wurari. In 1596, Sir Walter Raleigh referred to curare in The Discovery of the Large, Rich, and Beautiful Empire of Guiana. In 1780, Abbe Felix Fontana identified the action of curare on voluntary muscles. In 1800, Alexander von Humboldt described the extraction of curare. In 1811, Sir Benjamin Collins Brodie determined that complete recovery from curare poisoning is possible provided artificial ventilation is maintained. In 1825, Charles Waterton brought curarep to Europe, and in 1835 Sir Robert Hermann Schomburgk classified and named the vine Strychnos toxifera. In 1850, George Harley demonstrated that curare could be used to treat tetanus and strychnine poisoning. By 1868, Claude Bernard and Alfred Vulpian had identified the site of action of curare as the motor end plate. From 1887, curare was marketed for medical use by Burroughs Welcome. In 1900, Jacob Pal recognized that physostigmine could be used to antagonize the effects of curare. In 1912, Arthur Lawen demonstrated the use of curare during surgery, but this potential was not realized as the finding was published in German. In 1914, Henry Hallett Dale described the action of acetylcholine. In 1935, Harold King isolated D-tubocurarine and described its structure, while in 1936 Dale revealed the role of acetylcholine in neuromuscular transmission and the mechanism of action for curare. In 1940, Abram Elting Bennett revealed that curare could be used to reduce trauma during metrazol-induced convulsive therapy for spastic disorders in children. In 1942, Harold Griffith and Enid Johnson used curare to augment general anesthesia when performing an appendectomy. Curare was used surgically until the development of safer synthetic neuromuscular blocking analogues 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 in water 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/dart poison by indigenous South Americans. Later, curare was used as a muscle relaxant during surgery. Previously, to enable deep surgery, increased relaxation could only be achieved by higher and hence riskier quantities of general anesthetic. Being able to control the degree of muscle relaxation independently of the depth of sedation greatly improves survival, although bringing an 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, and subcutaneous routes. Human toxicity: Large doses and overdoses may cause respiratory paralysis and hypotension. When heated to decomposition it emits very toxic fumes of NOx and Cl-. Used as a muscle relaxant.

Environmental Fate

D-Tubocurarine acts as a non-depolarizing competitive antagonist at nicotinic acetylcholine receptors on the motor end plate of the neuromuscular junction, causing the relaxation of skeletal muscle. D-Tubocurarine competes with at least an equal affinity to acetylcholine, and at the same position on nicotinic receptors. Hence curare does not affect cardiac muscle, smooth muscle, or glandular secretions. Flaccid paralysis begins within a minute and progressively prevents movement of the eyes, limbs, and finally trunk. Death due to respiratory paralysis can occur 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.]

D-TUBOCURARINE CHLORIDE(57-94-3)Related Product Information

• 4-Methoxyphenethylamine
• 7-METHOXY-1,2,3,4-TETRAHYDRO-ISOQUINOLINE
• (S)-7-METHOXY-1-METHYL-1,2,3,4-TETRAHYDRO-ISOQUINOLIN-6-OL
• 3-METHOXY-N-METHYLBENZYLAMINE 97
• P-HYDROXYMETHAMPHETAMINE
• dimetamfetamine
• (S)-(-)-N,N-DIMETHYL-1-PHENETHYLAMINE
• 3-PHENOXYPHENOL
• 2,2'-DIHYDROXYDIPHENYL ETHER
• (R)-(+)-N,N-DIMETHYL-1-PHENYLETHYLAMINE
• D-TUBOCURARINE CHLORIDE
• 5-HYDROXYDOPAMINE HYDROCHLORIDE
• 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride
• 1-BENZYL-6,7-DIMETHOXY-1,2,3,4-TETRAHYDROISOQUINOLINE HYDROCHLORIDE
• Benzyltrimethylammonium chloride
• dimethyltubocurarinium chloride
• 3-(2-aminopropyl)phenol
• 3-HYDROXY-4-METHOXYPHENETHYLAMINE HYDROCHLORIDE