Curare side effects

A frequently cited example of an important natural-product-derived drag is the neuromuscular blocker d-tubocurarine, derived from the South American plant curare, which was used by South American Indians as an arrow poison (see Chapter 26). Tubocurarine led to the development of decamethonium, which, although structurally dissimilar to tubocurarine, was nevertheless synthesized based on the then prevalent presumption that tubocurarine contained two quaternary nitrogens. Similarly, synthetic local anesthetics, such as lidocaine, benzocaine, and dibucaine, were synthesized to mimic the nerve-blocking effect of cocaine, a natural alkaloid obtained from the leaves of Coca eroxylum, but without the adverse side effects that have led to its abuse. 

Physostigmine has limited medicinal use since it has serious side-effects, and as a result it has only been used in the treatment of glaucoma. However, simpler analogues have been made and have been used in the treatment of myasthenia gravis and as an antidote to curare. These analogues retain the important features mentioned above. Miotine (Fig. 11.51) still has the necessary carbamate, aromatic, and tertiary... 

Waser (20) suggested that toxiferine I and, perhaps, C-curare I might be clinically useful, since they have prolonged paralyzing actions and are relatively devoid of side effects. Preparations (curarine) which contain these active alkaloids have been used in man, but not enough of the pure alkaloids has been available for investigations. 

J. de Castro, A. Van de Water, L. Wouters, R. Xhonneux, R. Reneman and B. Kay, Comparative study of cardiovascular, neurological and metabolic side effects of 8 narcotics in dogs. Pethidine, pirimamide, morphine, phenoperidine, fentanyl, R 39 209, sufentanil, R 34 995. III. Comparative study of the acute metabolic toxicity of the narcotics used in high and massive doses in curarized and mechanically ventilated dogs, Acta Anaesthesiol. Belg., 1979, 30, 71-90. 

Somewhat later than (H-)-tubocurarine and following the studies of Stry-chnos curare alkaloids, toxiferine underwent clinical trials and was found to be rather more potent and fairly free from side effects, but its very long duration of action and its instability in solution precluded clinical exploitation of the alkaloid (485). However, modification of the toxiferine molecule by replacing the two iVb-methyl groups with JVb-allyl functions produced the semisynthetic compound alcuronium (4g), or Alloferin (267, 508), which is still in use as a short-lasting muscle-relaxant in minor surgery. It is obtained by semisynthesis from strychnine via Wieland-Gumlich aldehyde and subsequent quaternization with allyl bromide. See further. Bowman (485 pp. 139-140). 

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