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ACMT Toxicology Visual Pearl: Marcel the Shell with Toxins

Aaron Frolichstein, MD |

cone snail shell botulinum

The venom from this pictured snail shares a primary mechanism of action with what other deadly toxin?

  1. Alpha-latrotoxin
  2. Botulinum toxin
  3. Bufotoxin
  4. Tetanus toxin
  5. Sarin

Answer: 3. Botulinum toxin

The cone snail contains alpha-conotoxin which is a potent nicotinic receptor antagonist similar to botulinum toxin and can cause muscular paralysis.


The image above is of Conus striatus, a species of cone snail from the Conus genus, which contains over 800 different types of marine venomous snails. They primarily live in tropical waters such as islands in the Pacific, Caribbean, and Indian oceans, however there are some species that inhabit the Florida coast [1]. Each produces approximately 1,000 bioactive peptides, some of which are being studied as potential therapeutic agents [2].

Envenomation occurs when the attractive shell is picked up and the snail deploys its venom though its proboscis.

What are the symptoms of cone snail envenomation? [1, 3]

  • The clinical effects of envenomation vary widely based on the species and peptides involved.
  • Envenomation site:
    • Localized pain: May be both immediate and delayed pain
    • Local numbness, ischemia, cyanosis, and necrosis may occur.
  • Systemic symptoms:
    • Initially may include weakness, visual changes such as diplopia, and sweating
    • Later may progress to muscle paralysis, respiratory failure, cardiovascular collapse, and coma.
    • Cardiac arrhythmia is rarely reported
    • Although exceedingly rare, death has occurred within 6 hours primarily due to respiratory collapse
  • Clinical improvement typically occurs within 6-8 hours.

What is the mechanism of envenomation? [2, 4-8]

  • Alpha-conotoxin is an acetylcholine channel receptor antagonist which results in paralysis and is found in almost all species of cone snails [4].
    • Ziconotide is a non-opioid analgesic that has been FDA-approved for intractable pain and was derived from alpha-conotoxin [2]
  • Other agents identified in cone snail venom include:
    • Norepinephrine transporter antagonist isolated from the Conus marmoreus [5]
    • N-methyl-d-aspartate (NMDA) receptor antagonist from Conus geographus [6]
    • Potassium channel blocker from Conus purpurascens [7]
    • Insulin-like peptide identified in Conus geographus [8]

How do you treat cone snail envenomation? [3]

  • Treatment is largely supportive.
    • Hot water immersion: May provide some pain relief but the majority of conotoxins are heat stable
    • Remove the cone snail’s “radula” or envenomation spike.
    • Appropriate wound care.
    • Prophylactic antibiotics have been used.
  • There is no antivenom for cone snail envenomation.
  • All patients should be observed for at least 6 hours post-envenomation for clinical effects.

Bedside Pearls

  • The cone snail is a venomous marine snail capable of causing toxicity to humans.
  • The clinical effects vary widely based upon the species of cone snail involved.
  • Local numbness, ischemia, cyanosis, and necrosis may occur, and systemic effects can include weakness, visual changes such as diplopia, muscular paralysis, and respiratory or cardiac failure.
  • Observe patients for at least 6 hours post-envenomation.
  • Most cases will require local wound care, infection prevention, analgesia, and symptomatic management.


  1. Kapil S, Hendriksen S, Cooper JS. Cone Snail Toxicity. In: StatPearls. Treasure Island (FL): StatPearls Publishing; January 2, 2023. PMID: 29262115
  2. Himaya SWA, Lewis RJ. Venomics-Accelerated Cone Snail Venom Peptide Discovery. Int J Mol Sci. 2018;19(3):788. Published 2018 Mar 9. doi:10.3390/ijms19030788 PMID: 29522462
  3. Kohn AJ. Human injuries and fatalities due to venomous marine snails of the family Conidae. Int J Clin Pharmacol Ther. 2016;54(7):524-538. doi:10.5414/CP202630 PMID: 27285461 
  4. Sandall DW, Satkunanathan N, Keays DA, et al. A novel alpha-conotoxin identified by gene sequencing is active in suppressing the vascular response to selective stimulation of sensory nerves in vivo. Biochemistry. 2003;42(22):6904-6911. doi:10.1021/bi034043e PMID: 12779345 
  5. Nielsen CK, Lewis RJ, Alewood D, et al. Anti-allodynic efficacy of the chi-conopeptide, Xen2174, in rats with neuropathic pain. Pain. 2005;118(1-2):112-124. doi:10.1016/j.pain.2005.08.002 PMID: 16154696
  6. Barton ME, White HS, Wilcox KS. The effect of CGX-1007 and CI-1041, novel NMDA receptor antagonists, on NMDA receptor-mediated EPSCs. Epilepsy Res. 2004;59(1):13-24. doi:10.1016/j.eplepsyres.2003.12.011 PMID: 15135163
  7. Lubbers NL, Campbell TJ, Polakowski JS, et al. Postischemic administration of CGX-1051, a peptide from cone snail venom, reduces infarct size in both rat and dog models of myocardial ischemia and reperfusion. J Cardiovasc Pharmacol. 2005;46(2):141-146. doi:10.1097/01.fjc.0000167015.84715.27 PMID: 16044024 
  8. Ahorukomeye P, Disotuar MM, Gajewiak J, et al. Fish-hunting cone snail venoms are a rich source of minimized ligands of the vertebrate insulin receptor. Elife. 2019;8:e41574. Published 2019 Feb 12. doi:10.7554/eLife.41574 PMID: 30747102

Author information

Aaron Frolichstein, MD

Aaron Frolichstein, MD

Department of Emergency Medicine
Carolinas Medical Center

The post ACMT Toxicology Visual Pearl: Marcel the Shell with Toxins appeared first on ALiEM.

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