Recovery from the lethal effects of saxitoxin: a therapeutic window for4-aminopyridine (4-AP)

Benton, Bernard J.; Keller, Shannon A.; Spriggs, David; Capacio, Benedict R.; Chang, Feng-Chi

doi:10.1016/s0041-0101(97)00158-x

Cited by 20 publications

(8 citation statements)

References 16 publications

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“…18,19 Moreover, a therapeutic effect of 4-AP has been used in human medical treatment, and its effect is enhanced by the presence of NaHCO 3 , suggesting that NaHCO 3 is involved in K + transport. 20 Other reagentsammonium chloride (NH 4 Cl), sodium acetate (CH 3 COONa) and calcium chloride (CaCl 2 ) -were also selected to investigate the influence of pH or Ca 2 + . In marine fish sperm, it has been reported that NH 4 Cl and CH 3 COONa are agents for increasing and reducing [pH] i , respectively.…”

Section: Introductionmentioning

confidence: 99%

“…The voltage‐dependent K + channel blocker 4‐aminopyridine (4‐AP) is a candidate for this purpose, 13–16 because K + plays an important role in the initiation of fish sperm motility, 4,17 and the inhibitory effects of 4‐AP on the function of the potassium channel have been reported 18,19 . Moreover, a therapeutic effect of 4‐AP has been used in human medical treatment, and its effect is enhanced by the presence of NaHCO 3 , suggesting that NaHCO 3 is involved in K + transport 20 . Other reagents – ammonium chloride (NH 4 Cl), sodium acetate (CH 3 COONa) and calcium chloride (CaCl 2 ) – were also selected to investigate the influence of pH or Ca 2+ .…”

Section: Introductionmentioning

confidence: 99%

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Role of sodium bicarbonate on the initiation of sperm motility in the Japanese eel

Tanaka¹,

Utoh²,

Yamada³

et al. 2004

Fisheries Sci

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In order to find out the role of sodium bicarbonate (NaHCO 3 ) on the initiation of sperm motility in the Japanese eel Anguilla japonica , interactions were investigated between NaHCO 3 and various reagents (K + channel blocker 4-aminopyridine [4-AP], ammonium chloride [NH 4 Cl], sodium acetate and calcium chloride [CaCl 2 ]) that could regulate internal factors (intracellular K + , intracellular pH [[pH] i ] and intracellular Ca 2 + ) in sperm motility. Contradictory effects of NaHCO 3 were observed (i.e. an inhibitory effect when 4-AP was absent and a promoting effect when 4-AP was present). Sodium bicarbonate inhibited the initiation of sperm motility in the Japanese eel. However, NaHCO 3 restored the motility of immotile sperm that 4-AP inhibited. The inhibitory effect of NaHCO 3 disappeared with the addition of NH 4 Cl, which raised [pH] i , but the promoting effect was not affected by [pH] i . Although NaHCO 3 recovered motility in the presence of 4-AP, this recovery was also observed with the addition of CaCl 2 instead of NaHCO 3 . In the initiation of sperm motility in the Japanese eel, two roles for NaHCO 3 are suggested: an inhibitory role relating to the regulation of [pH] i and a promoting role relating to the uptake of another initiation factor, which could be Ca 2 + .

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Role of sodium bicarbonate on the initiation of sperm motility in the Japanese eel

Tanaka¹,

Utoh²,

Yamada³

et al. 2004

Fisheries Sci

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“…The developmental drug 4-aminopyridine has been found in animal studies to protect, if not counteract, the effects of both STX and TTX (Benton et al 1998), reversing the loss of blood pressure in experimental animals and enhancing neuromuscular transmission to allow their diaphragm to work. This may be more likely to be achieved if the displacer were an allosteric inhibitor that prevents toxin binding but from a site on the sodium channel distant from that of STX or TTX.…”

Section: Antitoxinsmentioning

confidence: 99%

Biological Toxins and Bioterrorism

Gopalakrishnakone¹,

Balali-Mood²,

Llewellyn³

et al. 2015

Toxinology

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In recent years, the field of toxinology has expanded substantially. On the one hand it studies venomous animals, plants and micro organisms in detail to understand their mode of action on targets. While on the other, it explores the biochemical composition, genomics and proteomics of toxins and venoms to understand their three interaction with life forms (especially humans), development of antidotes and exploring their pharmacological potential. Therefore, toxinology has deep linkages with biochemistry, molecular biology, anatomy and pharmacology. In addition, there is a fast-developing applied subfield, clinical toxinology, which deals with understanding and managing medical effects of toxins on human body. Given the huge impact of toxin-based deaths globally, and the potential of venom in generation of drugs for so-far incurable diseases (for example, diabetes, chronic pain), the continued research and growth of the field is imminent. This has led to the growth of research in the area and the consequent scholarly output by way of publications in journals and books. Despite this ever-growing body of literature within biomedical sciences, there is still no all-inclusive reference work available that collects all of the important biochemical, biomedical and clinical insights relating to toxinology. Composed of 11 volumes, Toxinology provides comprehensive and authoritative coverage of the main areas in toxinology, from fundamental concepts to new developments and applications in the field. Each volume comprises a focused and carefully chosen collection of contributions from leading names in the subject.

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“…Other pharmaceuticals may however be useful in counteracting the effects of STX or TTX. The developmental drug 4-aminopyridine has been found in animal studies to protect, if not counteract, the effects of both STX and TTX (Benton et al 1998), reversing the loss of blood pressure in experimental animals and enhancing neuromuscular transmission to allow their diaphragm to work. Large doses were required in these experiments, enough to potentially cause serious side effects, which could be ameliorated if the treatment occurs in a hospital, eventually saving the victim's life.…”

Section: Antitoxinsmentioning

confidence: 99%

Marine Biotoxins in History: Misuse and Mayhem

Llewellyn

2014

Toxinology

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Saxitoxin (STX) and tetrodotoxin (TTX) have a colorful history. Two of the most toxic natural toxins known, they have been used as weapons to commit suicide, attempt, or successfully commit murder, and STX has been officially declared a chemical weapon by the world's governments. This meant that it was no longer a natural marine chemical of interest to toxinologists, pharmacologists, and at times seafood producers (because it can taint their product); it had now come upon the radar of many government agencies. TTX has its own mystique more renowned as the toxin of "fugu" fame, but also been blamed as the active agent in the zombification rituals in some Caribbean cultures. However, deliberate intoxications by these toxins remain far fewer than accidental deaths through eating poorly prepared fugu meals or saxitoxin-infested shellfish. Diagnosis, rather than detection, remains the best means of identifying whether a victim has been purposefully intoxicated. Treatment of intoxication by STX or TTX is still relatively crude, relying mostly upon gastric evacuation to remove unabsorbed toxin and symptomatic relief to nurse the victim through the acute phase of an intoxication and then relying upon the body's natural recovery mechanisms. Some potential pharmaceutical treatment options exist, but these have only been tested in small mammal studies, upon few test animals, and under limited conditions and would require significant investment in resources to progress them beyond the laboratory.

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Recovery from the lethal effects of saxitoxin: a therapeutic window for4-aminopyridine (4-AP)

Cited by 20 publications

References 16 publications

Role of sodium bicarbonate on the initiation of sperm motility in the Japanese eel

Role of sodium bicarbonate on the initiation of sperm motility in the Japanese eel

Biological Toxins and Bioterrorism

Marine Biotoxins in History: Misuse and Mayhem

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