Paralytic compounds

Finally, chance observation led to the isolation of new paralytic compounds, asperparalines A, B, and C, from Aspergillus japonicus ATCC 204480. Asperparalines have unique structures consisting of a bicyclo[2,2,2]diazaoctane core and a spiro-succinimide moiety. 

Some dinoflagellates of the genus Alexandrium produce neurotoxic compounds known as paralytic shellfish poisoning (PSP) toxins. Because these toxins can contaminate filter-feeding shellfish they may threaten public health and create economic problems for fisheries. PSP-toxins include at least a dozen saxitoxins, neosaxitoxins, and gonyautoxins (Scheme 1). 

Historically, the first effective pharmacologic agents for lowering the blood pressure were the ganglionic blockers. At the level of the ganglia, these compounds block both sympathetic and parasympathetic transmission. The decrease in parasympathetic function is responsible for urinary retention, for the failure to develop an erection in the male patient and for the paralytic ileus. 

Preference is obviously for a simple chemical assay for PSP. Unfortunately the more specific the chemical test, the narrower is the window of compounds it can assay. The Paralytic Shellfish Poison is not just Saxitoxin (STX) as originally believed, but is a mixture of compounds closely related to STX Q) and the mix varies widely with location and with time ( ). It would seem, therefore that a chemical assay should determine at least the ratios of the several compounds, and that the relative toxicity of each of the compounds must be known. An effective assay must evaluate the actual biological toxicity of the shellfish being tested. For the chemical assay this requires the summated toxicity of all the... 

The main genera responsible for freshwater toxic blooms are Microcystis, Anabaena, Aphanizomenon and Oscillatoria. Toxins produced include 1. anatoxins, alkaloids and peptides of Anabaena 2. the peptide microcystin and related peptides of Microcystis 3. aphantoxins, compounds of Aphanizomenon with properties similar to some paralytic shellfish poisons. Properties of Oscillatoria toxin suggest they are peptides similar to those of Microcystis. Microcystis toxins are peptides (M.W. approx. 1200) which contain three invariant D-amino acids, alanine, erythro-3-methyl aspartic and glutamic acids, two variant L-amino acids, N-methyl dehydro alanine and a 3-amino acid. Individual toxic strains have one or more multiples of this peptide toxin. The one anatoxin characterized is a bicylic secondary amine called anatoxin-a (M.W. 165). The aphantoxin isolated in our laboratory contains two main toxic fractions. On TLC and HPLC the fractions have the same characteristics as saxitoxin and neosaxitoxin. 

In this study, suckling mice were inoculated with an echovims and if untreated they developed a fatal paralytic illness. When treated either prophylactically or within a few days of the viral inoculation, virtually all of the mice were protected. This is dramatic proof of the concept that these compounds can inhibit picornaviral infection in vivo. 

Paralytic Shellfish Poisoning (PSP) was first determined to be a problem in 1942 after three people and many seabirds died from eating shellfish on the west coast of the United States, near the Columbia River. It is caused by the saxitoxin family (saxitoxin + 18 related compounds) produced by several species of Alexandrium dinoflagellates. The main contamination problems include mussels, clams, crabs, and fish of the Pacific Northwest and Northeast Atlantic. 

The pharmacological properties of P-erythroidine and its dihydro derivative are very similar to those of d-tubocurarine and therefore need not be described in any detail. The two compounds differ from curare in three important respects, namely, less potent paralytic action on neuromuscular junctions, briefer duration of paralysis, and oral efficacy. Indeed, gastrointestinal absorption of the alkaloids is so rapid and complete that the difference between effective oral and subcutaneous doses is rather small. Dihydro-P-erythroidine is longer acting than P-erythroidine and about six times as active. Similar to curare, P-erythroidine and its dihydro derivative are antagonized at the neuromyal junction by anticholinesterases such as neostigmine. 

IPC is also effective for pharmacology related to brain disease. It was used to analyze picolinic acid and related compounds [90], neurotoxins associated with paralytic shellfish poisoning [91], a drug candidate for treating Alzheimer s disease [92], and nicergoline, clinically used for improving brain metabolism [93]. Quaternary ammonium anticholinergics were determined in whole blood and the matrix effect was taken into account [94]. 

Opiate-Related Agents Opiate-related agents are synthetic compounds similar to opiates. Side effects are nausea, vomiting, drowsiness, abdominal distention, Tachycardia, paralytic ileus, urinary retention, decreased secretions, and physical dependence. Two common opiate-related agents are ... 

DETERMINATION OF PROTEIN COMPLEXED PARALYTIC SHELLFISH POISONING. MECHANISM OF THE REMEDIATION (DETOXIFICATION) OF CHEMICALS (PESTICIDE, HEAVY METALS, OTHER TOXIC CHEMICAL COMPOUNDS)... 

Two naturally occurring compounds have been shown to contain a pyrrolol 1,2-clpyrimidine ring system. Saxitoxin. a paralytic poison isolated from certain shellfish, has been investigated by several groups.81 92,91 It has a complex structure that has been degraded through exhaustive reduction to 3-methyl- 1-oxo- 1,5,6,7-tetrahydropyrrolol 1,2-clpyrimidine (122). Synthesis of the isomeric 4-methyl derivative by Irino,9 and demonstration of its nonequivalence to the product isolated... 

Inorganic ions are presumed to be the smallest in the mixture, and hence their elution should be expected to be retarded the most. This, however, is not always the case because there are unpredictable interactions between the compounds and column support, such that the predicted elution order can often be reversed. These interactions can hold advantages for the extractor and can be used to isolate specific t3 es of compounds. The purification of paralytic shellfish toxins such as saxitoxin and gonyautoxins was done by taking advantage of their specific adsorption on Bio-Gel P-2 of Sephadex G-10. 

In the 1980s, our group began to screen microbes for insecticidal compounds that could be used in practice, or become lead compounds for the generation of new carbon skeletons. As a result, various strains were found to exhibit insecticidal, convulsive and paralytic activities against silkworms. This chapter deals with the procedures used for isolation of bioactive strains and their active principles. An overview of their chemical structures, activities, synthesis, and structurally related compounds is also given. 

---