How Does Curare Work?

When the Spanish Conquistadores began invading deep into South America, they died mysteriously, felled by blow darts and arrows that had even struck near vital structures. These 15th-century conquerors had no time to learn what poison had killed them. Perhaps they felt the horrible effect curare has on its victims: It paralyzes skeletal muscles. With the voluntary muscles crippled, the soldiers asphyxiated. It took 500 years after the Conquistadors for curare’s mystery to be unraveled. Understanding curare required the long and painstaking efforts of many nations of explorers, botanists, ship traders, biologists, physicians and an Italian Nobel Prize pharmacologist. Who could have imagined this powerful poison--which still brings down game in the Amazon--was, until recently, also saving patients in the operating room?

No one knows how curare was first discovered. “Curare” originates from the South American name for arrow poison, from the word, "ourare" or “woorari.” Aboriginal people still produce curare the way it was first documented in the 14th century. The two main plant sources in the jungle are from the Menispermaceae (Moonseed) family and from the Loganiaceae family. The woody plants are, respectively, Chondrodendron tomentosum and Strychnos toxifera. These woody vines and roots are crushed and boiled down to a thick, gooey black paste that resembles a shiny resin. Curare is only hazardous in the bloodstream, not swallowed by mouth. Therefore, experienced Amazonian poison makers can safely taste the curare, judging how intense it is from its degree of bitterness. Another way the potency of curare is tested is by shooting the poison into a frog and seeing how many times it hops before the frog stops moving. Once the potent paste is ready, the tips of darts and arrows are coated with the substance. Hunters must be careful not to cut or scrape themselves with the dangerous tips, lest they become the victims.

In 1812, scientists realized curare didn’t kill. In fact, if, you kept an animal alive by supporting its breathing long enough, it would recover completely. An animal just needed a few hours until its breathing muscles regained a non-paralyzed state, and the creature was as healthy as it had ever been. In 1856--from samples offered by Brazilian emperor Pedro II--physiologist Claude Bernard made a giant leap in understanding curare’s effect: It causes voluntary muscle paralysis by blocking impulse transmission between nerves and skeletal muscle. It doesn't paralyze smooth muscle at all (the type of muscle found in the heart, or intestinal tract).
A chemical named acetylcholine stimulates muscle. Acetylcholine transmits its orders though a chemical junction between the nerve and muscle; the spark of reaction between nerve and muscle sets up communication over and again in what is termed an “Action Potential.” Curare attaches to this junction, actually blockading this transmitting material, impeding future action potentials and making it insensitive to the action of acetylcholine. Until curare disintegrates, the nerve cannot trigger the muscle to act and the muscle stays paralyzed.

Curare is made up of very large molecular compounds, which also carry strong electrical charges. Therefore, curare can't get through the digestive system and can only be absorbed through a cut or wound directly into the bloodstream. Thus, eating an animal just killed with curare is harmless.

Synthetic forms of curare are used today. In the 1940s though the 1960s, curare was of great benefit--especially in anesthesia (as well as in conditions such as tetany and other spastic conditions). Before the use of curare, very deep anesthesia was required to relax a patient enough to perform upper abdominal surgery. Large, dangerous amounts of ether or chloroform were otherwise needed to try to relax these deep muscles. Even halothane, at such doses, caused fatal drops in blood pressure. Curare, because it relaxed the muscles, permitted a lighter dose of general anesthesia and did not doom elderly patients or those with bad hearts to the severe risks assumed with deep general anesthesia. Curare has since been replaced with manufactured muscle relaxants, but it pointed the way to a new era of safety in the field of anesthesia.