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Drug Discovery in Snake Venom

The deadly black mamba snake carries potent analgesics in its venom. These “mambalgins” were identified through a drug discovery screen of many venoms.

The black mamba’s venom is so potent that one bite spells almost certain death, in the absence of antivenom. At least the snake provides the courtesy of a potent analgesic to its victims, to go along with the potent neurotoxin carried in its venom.1 The venom of the black mamba is another example in which scientists are successfully drawing on Mother Nature for drug discovery, this time in the field of pain relief.
These peptides were found by screening animal venoms for new blockers of acid-sensing ion channels (ASICs), which are known to be key players in the pain pathway of humans. The two newly discovered peptides, termed mambalgins, belong to a family of three-finger toxins.2 They inhibit all ASIC subtypes expressed in the central nervous system, as well as ASIC subtypes expressed peripherally.2 This means that, unlike other related ASIC inhibitors, they can block pain both centrally and peripherally.
In terms of safety and relative efficacy, the mambalgins are as potent as morphine, but don’t have an associated risk of respiratory distress.1 Tolerance is a major problem in pain management, as patients become desensitized to analgesics. The mambalgins were associated with a slower buildup of tolerance. Together, these findings make the black mamba venom a promising new resource for drug discovery.
In addition to leading to new drug discovery, the peptides contained within black mamba venom may help researchers understand pain pathways. There is another ASIC inhibitor that was found in nature, the spider peptide toxin psalmotoxin 1 (PcTx1), which acts differently than the mambalgins.1 PcTx1 inhibits different ASIC channels and only acts on the central nervous system. By comparing the action and structures of different naturally derived ASIC inhibitors, it may be possible to dissect pain pathways for better pain management.

The black mamba isn’t the only creature that carries pain relievers in its venom. The cone snail does, too, and it has been taken to pill form.3 Nature is ripe with surprises, and continues to be a boon to the field of drug discovery.

  1. A. Flemming. Analgesics: Deadly snake venom for pain relief? Nature Reviews Drug Discovery 11, 906-907 (December 2012) doi:10.1038/nrd3897
  2. S. Diochot, et al. Black mamba venom peptides target acid-sensing ion channels to abolish pain. Nature 490, 552-555 (25 October 2012) doi:10.1038/nature11494
  3. Snail Venom Inspires Powerful Pain Reliever. Discovery News, Feb 11 2013.