Tubocurarine chloride is the only naturally occurring neuromuscular
blocking agent. It is derived from the bark of the South American plant
chondrodendron tomentosum, which has been used for centuries by South
American Indians as an arrow poison. I t was the first non-depolarising
neuromuscular blocking agent to be used in humans. I t has a marked
propensity to produce histamine release and thus hypotension, with possibly
a compensatory tachycardia. Historically, tubocurarine, alcuronium and
gallamine have been used in clinical practice, but they are no longer available
in the UK. A lcuronium chloride is a semisynthetic derivative of toxiferin, an
alkaloid of calabash curare. Gallamine triethiodide is a trisquaternary amine.
It was first used in France in 1948. The only recent use of gallamine in the UK
was as a small pretreatment dose (10 mg) before suxamethonium.
white to slightly yellowish powder
Tubocurarine is used mainly in anesthesiology as a myorelaxant, causing prolonged
muscle relaxation during an operation. Small doses are successful at causing temporary
relaxation of skeletal muscle without any vital change of primary body functions. It is used
particularly in endotracheal intubation or orthopedic surgery for repositioning fractures,
resetting compound dislocations, and so on. The main synonyms are tubarine and curarine.
muscle relaxant (skeletal)
The initial step involves extraction of the stems and bark of the plant
Chondrodendron tomentosum with water as the solvent.
Producing substantially pure d-tubocurarine chloride essentially comprises
treating with picric acid the quaternary-base fraction of a crude curare of the
curarine type, hydrolyzing the resulting picrate in an emulsion of hydrochloric
acid and a water-immiscible organic solvent for picric acid, recovering
crystalline d-tubocurarine chloride from the aqueous phase, dissolving the d_x0002_tubocurarine chloride in a minimum of hot water, allowing the solution to
stand at room temperature until the bulk of the d-tubocurarine chloride
precipitates, adding sufficient concentrated hydrochloric acid to bring the HCl
content up to about 6% and refrigerating the solution.
Tubocurarine chloride,( )-tubocurarine chloride hydrochloride pentahydrate, isprepared from crude curare by a process of purification andcrystallization. Tubocurarine chloride occurs as a white oryellowish white to grayish white, odorless, crystalline powderthat is soluble in water. Aqueous solutions of it are stableto heat sterilization.
The structural formula for (+)-tubocurarine was longthought to be that of Ia (see structure diagram). Throughthe work of Everett et al.,the structure is now knownto be that of Ib. The monoquaternary nature of Ib thusrevealed has caused some reassessment of thinking concerningthe theoretical basis for the blocking action, becauseall had previously assumed a diquaternary structure(i.e., Ia). Nevertheless, this does not negate the earlierconclusions that a diquaternary nature of the molecule provides better blocking action than does a monoquaternarynature (e.g., Ib is approximately fourfold lesspotent than dimethyl tubocurarine iodide). Further, (+)-isotubocurarine chloride (Ic) has twice the activity of Ib inthe particular test used.
Tubocurarine is a muscle relaxant and a nicotinic acetylcholine receptor antagonist. It can induce neuromuscular blocking.
