Historically, it has been used as an arrow poison by indigenous peoples in South America for its neuromuscular blocking properties, allowing them to paralyze animals during hunting, but also possibly kill due to paralysis of the respiratory muscles.
[3] The preparation of curare poisons involves complex rituals wherein the tribes extract toxins from various plants.
[4] They managed to produce only a couple micrograms of this compound as it is quite hard to isolate in large enough quantities to study.
[3] Curares like tubocurarine were later used as anesthetics in medical procedures, but were replaced in the 1960s by synthetic curare-like drugs like alcuronium, pancuronium, atracurium and vecuronium.
[6] Toxiferine is most commonly known for its use as an arrow poison alongside other curares by south american tribes.
Synthetic alternatives like alcuronium can and are still used in anesthetics due to their relatively shorter duration of action and fewer side effects.
It is also believed that because of its activity as muscle paralyzer, it can retain glycogen and ATP from releasing after death and by this delay rigor mortis.
The prevention of sodium influx leads to an inhibition of depolarization of the post-synaptic membrane, which is a necessary step for muscle contraction.
[9] The quaternary ammonium salt that toxiferine and its analogues share with acetylcholine is thought to be the reason for the binding affinity to the AChRs.
[13] Neostigmine works by inhibiting acetylcholinesterase, increasing the acetylcholine concentrations so it can compete more with the non-depolarizing neuromuscular-blocking drug.
[16] Toxiferine is classified as a dimeric bisindole alkaloid because it is symmetrically constructed from two identical monomeric units, each containing an indole ring.
Though the main difference between the analogues are the side groups attached to the positive nitrogen atom, also called the quaternary ammonium ion.
It is this quaternary ammonium ion that both toxiferine and its analogues share with acetylcholine that gives them their specific affinity for these receptors.
[20][21] The dimeric subunits of toxiferine bear high similarity to strychnine and may be a related product of its biosynthesis.
Especially the intermediate Wieland-Gumlich aldehyde is very similar to the dimeric subunits of toxiferine, though this lacks the quaternary ammonium ion.
Toxiferine is known to enter the body in two different ways: either orally by ingestion or intravenously while applied to a sharp tip for killing purposes.
It was also found that toxiferine is distributed to tissues with a high acidic mucopolysaccharide content like intervertebral discs and cartilage of the ribs.
Bis-quaternary nitrogen compounds like toxiferine have shown to be dependent on their lipophilicity to be transported to sites in the liver.
Toxiferine has a strong receptor affinity, which together with the poor excretion makes it accumulate in the body rapidly after repeated administration.