Pinnatoxins' Deleterious Effects on Cholinergic Networks: From Experimental Models to Human Health

Mar Drugs. 2019 Jul 20;17(7):425. doi: 10.3390/md17070425.

Abstract

Pinnatoxins (PnTXs) are emerging neurotoxins that were discovered about 30 years ago. They are solely produced by the marine dinoflagellate Vulcanodinium rugosum, and may be transferred into the food chain, as they have been found in various marine invertebrates, including bivalves. No human intoxication has been reported to date although acute toxicity was induced by PnTxs in rodents. LD50 values have been estimated for the different PnTXs through the oral route. At sublethal doses, all symptoms are reversible, and no neurological sequelae are visible. These symptoms are consistent with impairment of central and peripheral cholinergic network functions. In fact, PnTXs are high-affinity competitive antagonists of nicotinic acetylcholine receptors (nAChRs). Moreover, their lethal effects are consistent with the inhibition of muscle nAChRs, inducing respiratory distress and paralysis. Human intoxication by ingestion of PnTXs could result in various symptoms observed in episodes of poisoning with natural nAChR antagonists. This review updates the available data on PnTX toxicity with a focus on their mode of action on cholinergic networks and suggests the effects that could be extrapolated on human physiology.

Keywords: Vulcanodinium rugosum; acute neurotoxicity; cyclic imines; human intoxication; myasthenia gravis; nicotinic acetylcholine receptors; pinnatoxins.

Publication types

  • Review

MeSH terms

  • Acetylcholine / metabolism
  • Alkaloids / chemistry
  • Alkaloids / toxicity
  • Animals
  • Dinoflagellida / chemistry*
  • Disease Models, Animal
  • Humans
  • Lethal Dose 50
  • Marine Toxins / chemistry
  • Marine Toxins / toxicity*
  • Muscles / drug effects
  • Muscles / innervation
  • Muscles / metabolism
  • Nicotinic Antagonists / chemistry
  • Nicotinic Antagonists / toxicity*
  • Paralysis / chemically induced*
  • Poisoning / etiology*
  • Receptors, Nicotinic / metabolism
  • Spiro Compounds / chemistry
  • Spiro Compounds / toxicity
  • Synaptic Transmission / drug effects
  • Toxicity Tests, Acute

Substances

  • Alkaloids
  • Marine Toxins
  • Nicotinic Antagonists
  • Receptors, Nicotinic
  • Spiro Compounds
  • Acetylcholine