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Evidence that Tetrodotoxin and Saxitoxin act at a metal cation binding site in the sodium channels of nerve membrane
in capillaries; these are succeeded by blebbing and swelling with a loss of cytoplasmic electron density and the disease process culminates in disruption of the endothelium followed by extravasation of red blood cells which can be found in the endomysium. The authors discuss these changes in the light of known chemical constituents in crotaline and viper venoms and their known pharmacological activities . G.R . HExnsasox, R., Rrrcx~, J. M. and Srtucxaxr, G. R. Evidence that Tetrodotoxin and Saxi toxin act at a metal cation binding site in the sodium channels of nerve membrane . Proc. rratrr . Acad. Sci., US .A . 71, 3936-40 (1974) . and Saxitoxin (STS were studied on intact garfish olfactory nerves and detergent solubilized extracts of theso nerves to determine the binding sites. The presence of divalent and trivalent CSt10I13 (La a+~ Er a+ , Sma+~ Be a+~ Mga+~ ~a+~ Sra+ and ]tea+ ) inhibit the binding of the toxins to solubilized membranes, as did the monovalent cations Li+, Tl+ and H+ . Competition of the toxins for their.binding site is reversible. The ability of lithium to reduce toxin binding is parallel to its ability to reduce TTX sensitive ion flux through the membrane of the intact nerve. The authors conclude that the toxins act at a metal cation binding site in the sodium channel and suggest that this is the site for cadons (normally Na+ ions) as they pass through membrane during the action potential. The dissociation constant for Li+ 0~1-0~2 M and > 0~6 M for Na+ indicates the weak binding necessary for rapid passage of sodium ions. H.R . TETRODOI'OXIN (TTX)
Bxowrr, J. H. Toxicology and Pharmacology of Yenoms from Poisonous Snakes. Charles C. Thomas, Springfield, Illinois, 184 pp . has attempted to peruse a literature which is admittedly a diffuse and di®cult one to evaluate, and amve at syntheses in the various areas which concern him in the preparation of this small text . To do this, however, his reading background has been too small and his initial viewpoint seems excessively nafve. For example, in discussing the yield of venom from Micrurus fulvius, the North American coral snake, he cites old data which indicate that the yield of venom from this snake in a single bite could not exceed a few milligrams and then concludes that its capacity to produce death in an adult is 'very doubtful' in spite of the deaths on record . He has revived the ancient myth that snakes have many microorganisms in their mouths which can induce symptoms that `mimic bites caused by the crotalids which inject a necrotising venom' . The author participates in an interesting fallacy by comparing antivenin to pharmacologic blocking agents pointing out that `it is common knowledge in pharmacology that many drugs (inhibitors) can block the action of other drugs, but not to the same degree, necessarily'. The comparison of immunological antisera to pharmacological blocking agents in the strict chemical sense is inappropriate. Antisera neutralize directly each individual antigen molecule and exert a relatively close to `all or none'effect with much greater structural specificity than that which can be exhibited by pharmacological compounds where transposition of a methyl group, etc. can render partial effectiveness. In nature, the stereospecificity of venoms and their Antsera comes close to an absolute relationship . Variations in the effectiveness of the antiserum are only encountered when the venoms of snakes other than those from which the antivenin was made are cross-reacted with the antiserum. In those cases it may be that only some of the antigen molecules will be present, and other toxins, those which were not present in the original antigen, may be present instead. These toxins have been characterized by many workers using different methods and preparations prepared in different ways in many countries over long periods of time. In addition, every worker in this field will acknowledge that these materials are notoriously variable as they are produced, even within a single species over the course of a year . Because of this a writer in this field must be prepared to develop a consensus based on his own experience and an extensive knowledge of the applicable literature, perhaps even `biased' in favor of those investigations known to be more recent or more thorough . The auWor of this volume does not do so. This volume will be of some value to those workers in the field who can take advantage of tabular information concerning spxies distribution, venom yield, toxicity (as given in the literature by various routes of administration) and some pharmacological information . 1t is weak, however, and often misleading, where the author draws conclusions or gives his own opinion. J.A .G . THE AU17iOR
TOXICON 1975 Vol. 13
Bxowrr, J. H. Toxicology and Pharmacology of Yenoms from Poisonous Snakes. Charles C. Thomas, Springfield, Illinois, 184 pp . has attempted to peruse a literature which is admittedly a diffuse and di®cult one to evaluate, and amve at syntheses in the various areas which concern him in the preparation of this small text . To do this, however, his reading background has been too small and his initial viewpoint seems excessively nafve. For example, in discussing the yield of venom from Micrurus fulvius, the North American coral snake, he cites old data which indicate that the yield of venom from this snake in a single bite could not exceed a few milligrams and then concludes that its capacity to produce death in an adult is 'very doubtful' in spite of the deaths on record . He has revived the ancient myth that snakes have many microorganisms in their mouths which can induce symptoms that `mimic bites caused by the crotalids which inject a necrotising venom' . The author participates in an interesting fallacy by comparing antivenin to pharmacologic blocking agents pointing out that `it is common knowledge in pharmacology that many drugs (inhibitors) can block the action of other drugs, but not to the same degree, necessarily'. The comparison of immunological antisera to pharmacological blocking agents in the strict chemical sense is inappropriate. Antisera neutralize directly each individual antigen molecule and exert a relatively close to `all or none'effect with much greater structural specificity than that which can be exhibited by pharmacological compounds where transposition of a methyl group, etc. can render partial effectiveness. In nature, the stereospecificity of venoms and their Antsera comes close to an absolute relationship . Variations in the effectiveness of the antiserum are only encountered when the venoms of snakes other than those from which the antivenin was made are cross-reacted with the antiserum. In those cases it may be that only some of the antigen molecules will be present, and other toxins, those which were not present in the original antigen, may be present instead. These toxins have been characterized by many workers using different methods and preparations prepared in different ways in many countries over long periods of time. In addition, every worker in this field will acknowledge that these materials are notoriously variable as they are produced, even within a single species over the course of a year . Because of this a writer in this field must be prepared to develop a consensus based on his own experience and an extensive knowledge of the applicable literature, perhaps even `biased' in favor of those investigations known to be more recent or more thorough . The auWor of this volume does not do so. This volume will be of some value to those workers in the field who can take advantage of tabular information concerning spxies distribution, venom yield, toxicity (as given in the literature by various routes of administration) and some pharmacological information . 1t is weak, however, and often misleading, where the author draws conclusions or gives his own opinion. J.A .G . THE AU17iOR
TOXICON 1975 Vol. 13