Curine curare

These results show that bebeerine is represented by (I Rj = R3 = H and Rj = R = Me). See also curine (Z-bebeerine), dealt with as a curare alkaloid (p. 374). 

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. 

These results seemed to establish with certainty that the active component of tube curare is derived from Chondrodendron tomentosum, but the matter again became doubtful when King reported that in the stems of a carefully authenticated specimen of the plant, collected at Tarapoto in Peru, he had found 1-curine and Z-tubocurarine chloride. This is the first recorded natural occurrence of the latter and seems to indicate either that the alkaloidal components of the plant are not constant in character, or that the botanical description of Chondrodendron tomentosum covers two species containing the dextro- and Icevo- quaternary alkaloids respectively. 

The process of isolation finally adopted by the former authors consists in precipitating as reineckates the water-soluble bases contained in a methyl alcoholic extract of the curare. The mixed reineckates are further purified, by solution in acetone and precipitation with water as often as may be necessary. The product so cleaned represents the bulk of the biological activity of the crude drug the mother liquors may contain curine (p. 374), which indicates a menisperm as one of the components of such curares. The mixed reineckates are then fractionated chromato-graphically over alumina and the components isolated as chlorides by the use of silver sulphate and barium chloride in succession. This process has been modified in detail by Schmid and Karrer, who have also found that with their curare, the more soluble reineckate fraction includes less potent quaternary alkaloids. 

The material first used by Wieland et al. was gourd curare from the middle Orinoco district, near Urbana, in Bolivar State, Venezuela, but in the fomth paper (1941) results are recorded for curares from Colombia and Venezuela, for which more precise details of origin are not available and there is considerable difference in the nature and quantity of the alkaloids in the various samples used. An examination has also been made of the bark of Strychnos toxifera, and one of the alkaloids (toxiferine II) it contains has been found in some of the curares examined. In all, ten alkaloids have been obtained and characterised and, with the exception of curine, they are all of quaternary type. They are named toxiferine, dihydrotoxiferine, or calabash-curarine (shortened to C-curarine in practice) according to type, and the variants within the type are distinguished by numbers, or numbers and letters, e.g., toxiferine I, toxiferine Ilb. 

Alkaloids of Curare Curine, Tubocurarine, Protocuridine, Calabash-curare I, etc., including Erythrina alkaloids Alkaloids of Ipecacuanha. ... 

The alkaloid content of curare is from 4% to 7%. The most important constituent in menispermaceous curare is the bis-benzyltetrahydroisoquinoline alkaloid (+)-tubocurarine (Figure 6.48). This is a monoquaternary ammonium salt, and is water soluble. Other main alkaloids include non-quaternary dimeric structures, e.g. isochondrodendrine and curine (bebeerine) (Figure 6.48), which appear to be derived from two molecules of (R)-N-methylcoclaurine, with the former also displaying a different coupling mode. The constituents in loganiaceous curare (from calabash curare, i.e. Strychnos toxifera) are even more complex, and a series of 12 quaternary dimeric strychnine-like alkaloids has been identified, e.g. C-toxiferine (toxiferine-1) (see page 359). 

The bisbenzylisoquinolines have been the subject of many pharmacological studies, motivated originally by the knowledge that quaternary alkaloids of this type are the active constituents of tube curare. Certain nonquaternary bisbenzylisoquinolines, notably belonging to the curine group, are also smooth muscle re-laxants many bisbenzylisoquinolines are hypotensive, and a few possess anti-... 

Tubocurarine.chondrocura- rine.curarine.isochondro- dendrine.curine Analysis curare... 

Curine is much less toxic than the other alkaloids of curare (73, 74, 78). It affects the conducting system and therefore has cardiac action. High concentrations of this alkaloid causes paralysis of the striated muscles and paralysis of the nerve end plates. 

In 1939 King (123) obtained both the leaves and liana of the plant amphi huasa (poison rope) which is used by the Indians near Tarapoto in northern Peru for the preparation of curare. It was identified as Chondrodendron tomentosum, and chemical examination showed that it contained Z-curine (Z-bebeerine) and Z-tubocurarine chloride and not d-tubo-curarine chloride as expected. However Wintersteiner and Dutcher (81)... 

Of the three alkaloids d-tubocurarine chloride, bebeerine, and curine (74, 76, 78, 80) the first has the strongest curarizing action. d-Tubocura-rine chloride produces complete paralysis of the frog when doses of 0.5 mg. per kilogram are administered (76). It seems to cause typical respiratory paralysis in mammals. LTubocurarine chloride is many times weaker in curariform activity than its enantiomorph d-tubocurarine chloride (123). 

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. 

Although alkaloids with curarizing activity usually are dimers, a monomeric alkaloid with curarizing activity, vene-curine (51), has been isolated from the curare prepared by the Hoti tribe of Venezuela (Quetin-Leclercq et al., 1989). 

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