Curare source

Bebeerine and its allies (p. 363) are also derived from menispermaceous plants, but as their botanical source needs attention in some detail, and in view of their importance as close associates of the curare alkaloids, they are dealt with separately at the end of this section. 

Para, Tube or Bamboo Curare. This variety was packed in sections of bamboo, but this almost traditional information needs modification since tube curare became a commercial article. It is now a viscous, solid or even powdered extract, exported in sealed tins. In view of the relationship established between bebeerine, curine, and tubocurarhie, the active alkaloid of this variety of curare, the suggestion was made, first by Spath, Leithe and Ladeck, and more definitely by King that its botanical source should be sought among the Brazilian Menispermaceae, and as shown later the search for the source of the d-tubocurarine found in this variety of curare has been narrowed down to Chondrodendron tomentosum, or possibly a closely related species liable to be confused with it. 

Alkaloids of Pot Curare. This variety of curare is a dark brown, comparatively dry extract. According to Boehm, it contains protocurine, colourless hair-like needles, m.p. 306° (dec.), a base of low toxicity and yielding crystalline salts. A second alkaloid of similar type is protocuridine prisms, m.p. 274-6°, sparingly soluble in all ordinary solvents. The poisonous constituent is protocurarine, a red powder, easily soluble in water, and giving characteristic colour reactions with nitric acid and with oxidising agents in sulphuric acid, this latter reaction indicating a Strychnos spp. as a possible botanical source. 

This is a pantropical and warm temperate family well represented in South America. It is the source of several types of curares and the drug strychnine, which is now primarily used as a rat poison. Some species are cultivated as ornamentals. 

The active principles of curare were early recognized to be water-soluble quaternary alkaloids. Tube-curare was studied by King, who isolated (3) the crystalline quaternary bisbenzylisoquinoline alkaloid, d-tubocurarine (I), in 1935. The main plant constituent of tube-curare is the bark of menispermaceous plants, particularly of the genus Chondro-dendron, and d-tubocurarine was later isolated (4) from C. tomentosum. Further work led to the isolation and structural elucidation of many more bisbenzylisoquinoline alkaloids from these sources (5). 

Curare was obtained from several sources but most commonly from the vine Chondrodenron tomentosiim. The explorers Humboldt and Bonpland in South America (1799-1804) reported that an extract of its bark was concentrated as a tar-like mass and used to coat arrows. The potency was designated one tree if a monkey, struck by a coated arrow, could only make one leap before dying. A more dilute ( three tree ) from was used to paralyse animals so that they could be captured alive - an early example of a dose-response relationship. 

Originally curare was a term used to describe collectively the very potent arrow poisons used since early times by the South American Indians. The arrow poisons were prepared from numerous botanic sources and often were mixtures of several different plant extracts. Some were poisonous by virtue of a convulsant action and others by a paralyzant action. Only the latter type is of value in therapeutics and is spoken of ordinarily as curare. 

As a potent muscle relaxant, curare can cause death quickly by inducing asphyxia due to rapid relaxation of diaphragmatic muscles. According to one source, death from respiratory arrest can take place within a few minutes in birds and small prey, and up to 20 min in larger mammals. Curare is considered to be highly toxic. The LD50 values are as follows ... 

In 1935, King (55) isolated a pure alkaloid, which he named d-tubocurarine, from a tube curare of unknown botanical origin. The word "tube" refers to the container in which the South American natives transported their plant extract. It was almost 10 years later that the botanical source for d-tubocurarine was clearly identified as Chondodendron tomentosum. The structure that King assigned to tubocurarine possessed two nitrogen atoms, both of which were quaternary ammonium salts (e.g., a b/s-quaternary ammonium compound). It was not until 1970 that the... 

A sample of curare was prepared by Indians of the upper Amazon under the supervision of a botanist in order to insure the plant source. The plant species was Chondodendron tomentosum and the curare thus obtained was a black paste called Serpa which represented a concentrated aqueous extract of the stems and bark (81). The desiccated extract contained five alkaloids (104), d-isochondodendrine, methylisochondodendrine, d-tubocurarine chloride, curine, and a new base to which the name d-chondocurine was given. 

Alexander von Humboldt (1769-1859) was the first to report that Strychnos toxifera Isa source of curare. Information about a South American vine, Chondro-dendron tomentosum, as another source had come from Hippolyto Ruiz and Joseph Pavonin 1794. 

Numerous bisindole alkaloids, formed by dimerization of monomeric monoterpenoid-derived indoles, have been isolated. Probably the best source of these alkaloids is Cathara-nthus roseus bisindole alkaloids from this source have been tabulated (Blasko and Cordell, 1990). Several of these alkaloids antitumor activity (Blasko and Cordell, 1988) most important in this regard are vincristine (55) and vinblastine (56) from Catharanthus roseus (Fig. 34.15). Certain other dimeric indole alkaloids known as curares have paralytic effects in animals (see the subsection Curares from Strychnos species, above). 

Curare is a muscle relaxant drug, originally used as an arrow poison by Amazonian Indians. The traditional curare is prepared by a secret recipe thought to involve a number of plant species (Plotkin 1993). Plant sources of curare include Strychnos castelnaei and species in the Loganaceae family and Chondodendron tomentosum in the Menispermaceae family. Tubocurarine, a benzylisoquinoline dimer, is the major alkaloid in the curare plants. It exhibits paralysing effects on skeletal muscles, and is used as a muscle relaxant in surgical procedures. It controls convulsions caused by the toxic alkaloid strychnine. 

To outline how this has come about, in other words, to examine the role of curare in the development of modern muscle relaxants, is the aim of the present review. But it is also concerned with the plants that are the sources of activity and with the substances that are their active principles. Certain aspects of the pharmacology, including the mode of action, of these compounds and the development of the muscle relaxants derived from them are also outlined. 

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