curare

curare , any of a variety of substances originally used as arrow poisons by Native South Americans in hunting and in warfare. The main active substance of curare, tubocurarine, is an alkaloid extracted from Chondodendron tomentosum, Strychnos toxifera, and other plant species. The poison produces muscle paralysis by interfering with the transmission of nerve impulses at the receptor sites of all skeletal muscle. Muscles with many nerves, such as eye muscles, are affected first. In recent years curare has been put to medical use. When given in small quantities with general anesthesia , especially in abdominal surgery, curare ensures the desired relaxation of muscle tissue with a minimal concentration of the anesthetic, lessening the possibilities of anesthesia-induced complications. Curare is also used to relieve spastic paralysis, to treat some mental disorders, and to induce muscle relaxation for the setting of fractures.

curare is the name of a crude drug, existing in the form of a dark brown, sticky, plant extract, and characterized by containing considerable amounts of poisonous alkaloids. Curare was prepared by the South American Indian tribes living in the valleys of the Amazon and the Orinoco. The extracts were used as arrow poisons, for hunting, in a way which demonstrates a profound understanding of mechanisms. The flesh of animals killed by a poisoned arrow could be eaten with impunity, showing that the poison was lethal when injected, but not absorbed when taken orally. History does not tell us just how many attempts to develop arrow poisons had less fortunate outcomes. When Westerners turned their attention to the nature of South American arrow poisons there were considerable problems in discovering the active principles. Individual samples from the same region were often variable in composition. In some samples several hundred constituents could be detected, mainly of plant origin, but often including animal material, such as excreta, and sometimes soil. Attention eventually focussed on extracts of plants from the families Menispermaceae, particularly Chondrodendron species, and Loganiaceae. Curare became available in three major forms with different regional origins: packed into bamboo tubes (tube-curare); in gourds (calabash-curare) containing material from Strychnos species; and in earthenware pots (pot-curare). In 1935 Harold King, a chemist working for the Medical Research Council in London, extracted, from a sample of tube-curare from the British Museum, a crystalline alkaloid which he called tubocurarine. This was to have a major impact in medicine.

Tubocurarine blocks the effects of the neurotransmitter acetylcholine in sites where it acts on the type of post-synaptic membrane receptors which are known as nicotinic. Quite the most important sites of these receptors are the junctions between motor nerves and voluntary skeletal muscle. When injected — and this includes injection by poisoned arrow — control of voluntary muscles is lost and flight or escape is not possible. Long before King had investigated the structure of tubocurarine, Claude Bernard had shown in 1856 that curare blocked neuromuscular transmission, without affecting conduction in the nerve or the contractility of the muscle. We now know that curare competes with acetylcholine for combination with the receptors on the muscle membrane — causing neuromuscular block.

In surgery, access to body cavities is hampered by tension in the voluntary muscles. These can be relaxed using anaesthetics, but only if dangerous dosage levels are used. Another, rather awkward solution is for assistants to hold open the incision with retractor. Motor paralysis by tubocurarine offered a surer and less cumbersome alternative. Use of such muscle relaxants became widespread for major surgery from the mid twentieth century. Not all voluntary muscles are equally sensitive to tubocurarine, and fortunately the respiratory muscles are the most spared. Thus by careful control of the dosage respiration can be maintained, although it is usual for anaesthetists to control the ventilation of the lungs mechanically.

For many years the commercial supply of tubocurarine was by extraction from crude curare extracts. New synthetic drugs, such as atracurium, have now largely replaced tubocurarine in medical practice. Nevertheless, for a while, surgery owed a debt to the experimentation of primitive peoples with their need for an arrow poison.

Alan W. Cuthbert

Bibliography

Sneader, W. (1985). Drug discovery — the evolution of modern medicines. Wiley, Chichester.

curare A resin obtained from the bark of South American trees of the genera Strychnos and Chondrodendron that causes paralysis of voluntary muscle. It acts by blocking the action of the neurotransmitter acetylcholine at neuromuscular junctions. Curare is used as an arrow poison by South American Indians and was formerly used as a muscle relaxant in surgery.