Laura Lorenz Mark Fischer Larvingo Alston. History Native South America tribes smeared a paste made from Chondrodendron tomentosum on blow darts and.

CURARE

Laura Lorenz

Mark Fischer

Larvingo Alston

History Native South America tribes smeared a paste made from

Chondrodendron tomentosum on blow darts and arrowheads to improve chances of obtaining wild game.

1595 was the first published account by Sir Walter Raleigh’s expedition up the Amazon.

1804 Alexander von Humboldt published the first recipe of Native South American’s poison, termed curare, woorari, or wourali.

Charles Waterton 1812Explored Guiana and Brazil Description of a donkey being revived by artificial respiration

after it had been poisoned with wourali, curare. 1935 Harold King isolated compound D-tubocurarine—residue

from ceramic pottery in British Museum

Richard Gill

Gill suffered from painful muscle spasms and he didn’t respond to treatment

1938 led a four month expedition to Ecuador He studied customs and traditions of indigenous

South American people He was appointed as a shaman within the tribe,

where he learned the technique and preparation of the toxin

He returned back to the United States with the recipe for curare and marketed it, but without success

1932 suffered neurological syndrome and muscle damage due to a horse accident which worsened over time

Chemical Structure of D-Tubocurarine

Normal Physiological Action Potential at Neuromuscular Junction

Pre-synaptic neurons contain voltage gated calcium channels

An action potential reaches the pre-synaptic bud causing the channels to open

Calcium ions to flow into the pre-synaptic bud Calcium ions cause vesicles to fuse with pre-

synaptic membrane releasing acetylcholine Acetylcholine diffuses across the synaptic cleft Acetylcholine binds to acetylcholine receptors in

the post-synaptic membrane causing sodium channels to open, sodium flows in

Depolarization of the post-synaptic membrane occurs

Threshold is reached action potential is initiated Acetylcholinesterase breaks down Acetylcholine

Competitive Antagonist of Acetylcholine

Curare binds to the acetylcholine receptor

Sodium channel does not open

No action potential propagated

Resulting in paralysis

Reversal Agents

Acetylcholinesterase inhibitors (Neostigmine, Pyridostigmine, edrophonium)

Hydrolyze acetylcholinesterase Acetylcholine concentration increases in

the synaptic cleft Acetylcholine displaces Curare on the

acetylcholine receptor

Curare Non-depolarizing Neuromuscular Blocking Agent (NMB) Curare prevents signal transduction Curare is the prototypical non-

depolarizing NMB Several more effective synthetic analogs

have since been produced (rocuronium, pancuronium, vecuronium)

Curare is rarely utilized in anesthesia today

Succinylcholine

Depolarizing neuromuscular blocking agent

Synthesized by attaching two molecules of acetylcholine together

Propagates signal transduction by activating acetylcholine receptor

Produces a prolonged depolarization Degraded by plasma

pseudocholinesterase

Ryanodine Receptor Propagated action potential

travels from the motor endplate through T-tubules

In T-tubules dihydropyridine receptors (DHPR) are activated and induce calcium influx

Calcium release leads to activation of Ryanodine receptor 1 (RyR1) in the sacroplasmic reticular (SR) membrane

Calcium release from SR yields excitation contraction coupling

Malignant Hyperthermia Autosomal dominant disease Mutation in DHPRs and RyR1 Causes leak in calcium when exposed to

succinylcholine and inhalation anesthetics Muscle rigidness, hyperkalemia,

arrhythmias, respiratory and metabolic acidosis, greatly increased body temperature

Treatment is with Dantrolene antagonist of RyR1

Conclusion Curare is derived from Chondrodendron

tomentosum Historically used by indigenous tribes for

hunting Active compound D-tubocurarine isolated Used as a non-depolarizing neuromuscular

blocking agent in anesthesia Prototype from which more effective non-

depolarizing NMBs have been synthesized

Bibliography Anderson, Rebecca. “A Tortured Path: Curare’s journey from poison darts to

paralysis by design.” Pubmed. 2010. 5. 252-258. http://www.ncbi.nlm.nih.gov/pubmed/21045238.

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