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