Neurotoxic Alkaloids: Saxitoxin and Its Analogs

Abstract

Saxitoxin (STX) and its 57 analogs are a broad group of natural neurotoxic alkaloids, commonly known as the paralytic shellfish toxins (PSTs). PSTs are the causative agents of paralytic shellfish poisoning (PSP) and are mostly associated with marine dinoflagellates (eukaryotes) and freshwater cyanobacteria (prokaryotes), which form extensive blooms around the world. PST producing dinoflagellates belong to the genera Alexandrium, Gymnodinium and Pyrodinium whilst production has been identified in several cyanobacterial genera including Anabaena, Cylindrospermopsis, Aphanizomenon Planktothrix and Lyngbya. STX and its analogs can be structurally classified into several classes such as non-sulfated, mono-sulfated, di-sulfated, decarbamoylated and the recently discovered hydrophobic analogs—each with varying levels of toxicity. Biotransformation of the PSTs into other PST analogs has been identified within marine invertebrates, humans and bacteria. An improved understanding of PST transformation into less toxic analogs and degradation, both chemically or enzymatically, will be important for the development of methods for the detoxification of contaminated water supplies and of shellfish destined for consumption. Some PSTs also have demonstrated pharmaceutical potential as a long-term anesthetic in the treatment of anal fissures and for chronic tension-type headache. The recent elucidation of the saxitoxin biosynthetic gene cluster in cyanobacteria and the identification of new PST analogs will present opportunities to further explore the pharmaceutical potential of these intriguing alkaloids.

Cyanotoxins in inland lakes of the United States: Occurrence and potential recreational health risks in the EPA National Lakes Assessment 2007

“…Saxitoxins are a group of at least 58 neurotoxins most commonly associated with paralytic shellfish poisoning (PSP) after consumption of seafood from marine environments (Wiese et al, 2010). Saxitoxins occurrence in freshwaters has been understudied, and there are several known producers amongst the freshwater cyanobacteria and include Anabaena sp., Aphanizomenon sp., Cylindrospermopsis sp., Lyngbya sp., Oscillatoria/Planktothrix sp., and Planktolyngbya sp.…”

“…Saxitoxins occurrence in freshwaters has been understudied, and there are several known producers amongst the freshwater cyanobacteria and include Anabaena sp., Aphanizomenon sp., Cylindrospermopsis sp., Lyngbya sp., Oscillatoria/Planktothrix sp., and Planktolyngbya sp. Saxitoxins are among the most potent group of natural mammalian neurotoxins known (Wiese et al, 2010;Cusick and Sayler, 2013). This class of toxins acts as calcium, potassium, and sodium channel blockers.…”

“…injection with saxitoxins ranging from 1 to 10 mg saxitoxin/kg bw (summarized Chorus and Bartram, 1999;Deeds et al, 2008;Botana et al, 2010). Saxitoxin analogue toxicity has been reported to range from equivalent to less than 1% compared to the toxicity of saxitoxin (Wiese et al, 2010).…”

On the occurrence and toxicity of Cylindrospermopsis raciborskii in Poland

“…STXs are neurotoxic alkaloids that block voltage-gated sodium channels in neuronal cells, also implicated in paralytic shellfish poisoning (O'Neill et al 2016). To date, over 55 analogues that vary in toxicity have been identified including non-sulfated, mono-sulfated, disulfated, decarbamoylated and hydrophobic variants (Wiese et al 2010).…”

Toxin profile change in vegetative cells and pellicle cysts of Alexandrium fundyense after gut passage in the eastern oyster Crassostrea virginica

“…saxitoxin and its derivatives (> 50 compounds with different toxicities). PSTs are perhydropurine alkaloids that share a tricyclic carbon backbone but differ in their functional groups at 4 positions (Schantz 1960, Wiese et al 2010. The transfer and accumulation of PSTs into commercially harvested shellfish soft tissues is a global human-health issue (Bricelj & Shumway 1998, Anderson et al 2002, Wang 2008) that is managed by toxin monitoring programs and harvesting bans when toxin limits are exceeded.…”