Spirolides and Cyclic Imines: Toxicological Profile

Abstract

In this chapter, available evidence on the toxicological profile of spirolides and other lipophilic cyclic imine toxins is reviewed, highlighting their chemical structure, the phytoplankton species involved in their production, their pharmacokinetics/toxicokinetics and experimental toxicity, and their molecular targets and mechanisms of action. These phycotoxins belong to an emerging class of chemical agents associated with marine algal blooms and shellfish toxicity. Their chemical structure is represented by a macrocycle, with the ring size between 14 and 27, and two conserved features that include the cyclic imine group and spiroketal ring system. The producers of spirolides, gymnodimines, and pinnatoxins have been identified as being the dinoflagellates Alexandrium ostenfeldii/peruvianum, Karenia selliformis, and Vulcanodinium rugosum. Their acute toxicity, appraised by the mouse bioassays, classifies them as "fast-acting" toxins because they induce rapid onset of neurological symptoms followed by death within a few minutes. The spirolide congeners are the most toxic after intraperitoneal injection, while there are indications that pinnatoxins are the most toxic group after oral administration. The neurotoxic effects reported for these phycotoxins are mostly due to their specific interaction with the muscle and neuronal types of nicotinic acetylcholine receptors which are the principal molecular targets of spirolides, gymnodimines, and pinnatoxins, so far studied. Hence, these phycotoxins exhibit both high affinity and broad specificity on nicotinic receptors, indicating that their sites of interaction in the receptors include amino acid residues highly conserved among animal species.