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PRINCIPLES OF TOXICOLOGY

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432 PROPERTIES AND EFFECTS <strong>OF</strong> NATURAL TOXINS AND VENOMS<br />

ment. Some of the toxins mentioned in this chapter are serving as molecular models for designing<br />

drugs with novel mechanisms of action. For instance, the worm toxin anabaseine has been modified<br />

to eliminate its peripheral nicotinic agonist activity, and the resulting compound, DMXB-anabaseine<br />

(also known as GTS-21), is now undergoing human clinical tests as a possible Alzheimer’s drug (Kem,<br />

1995).<br />

The goal of drug development is to sever the connection between toxicity and therapeutic activity<br />

of compounds intended as drugs, but this ideal is rarely completely attainable. It is useful to keep in<br />

mind that the difference between toxin and drug is often a seemingly minor alteration of chemical<br />

structure, or at the least, proper selection of dosage. The sixteenth-century physician and chemist<br />

Paracelsus understood the dual nature of Materia Medica when he stated that drugs are also poisons,<br />

and it is often a matter of dose whether the therapeutic or toxic effect predominates. For all the problems<br />

that natural toxins and venoms cause, our collective ability to use them as tools in biomedical research<br />

and drug design makes them valuable reagents in medical research. Ultimately, these substances can<br />

benefit, more than damage, human existence.<br />

17.9 SUMMARY<br />

A toxin is a single substance that adversely affects some biological process or organism, whereas<br />

a venom is a heterogeneous mixture of many substances, some of which are toxic. A poison is<br />

either a single injurious substance or a mixture of substances and can be human-made (synthetic)<br />

or natural.<br />

Knowledge of the mechanism by which a toxin acts on some biological process provides the<br />

ultimate basis for rational treatment of intoxication. While many protein intoxications are successfully<br />

treated by immunotherapy, treatment of smaller nonpeptide toxins must be based upon pharmacologic<br />

antagonism as well as symptomatic treatment. It is extremely important to identify the toxin or venom<br />

involved in an intoxication in order to select the appropriate treatment.<br />

Initial treatments, such as induction of vomiting, and gastric lavage, for orally ingested toxins and<br />

immobilization of individuals bitten by poisonous snakes or other animals can reduce entry of the<br />

toxin(s) into the systemic circulation, and thereby delay the onset and reduce the intensity of the<br />

response. Success often depends on the training of personnel responsible for initial care of the victim.<br />

While few human intoxications due to natural toxins or venoms are lethal when properly treated,<br />

delayed or inadequate treatment can be life-threatening.<br />

Toxins and venoms are not only potentially injurious to health but can also be beneficial in providing<br />

new research tools for biomedical research and unique molecular models for designing new drugs.<br />

ACKNOWLEDGMENTS<br />

The author thanks Barbara Seymour for artistic renderings of the poisonous organisms and Judy Adams<br />

for word-processing the manuscript.<br />

REFERENCES AND SUGGESTED READING<br />

Ames, B., M. Profet, and L. S. Gold, “ Nature’s chemicals and synthetic chemicals: Comparative toxicology,” Proc.<br />

Natl. Acad. Sci. (USA) 87: 7782–7786 (1990).<br />

Anderson, D. M., “Red tides,” Sci. Am. 271: 62–70 (1994).<br />

Auddy, B., M. I. Alam, and A. Gomes, “ Pharmacological actions of the venom of the Indian catfish (Plotosus canius<br />

Hamilton),” Ind. J. Med. Res. 99: 47–51 (1994).<br />

Daly, J. W., “The chemistry of poisons in amphibian skin,” Proc. Natl. Acad. Sci. (USA) 92: 9–13 (1995).<br />

Dickstein, E. S., and F. W. Kunkel, “Foxglove tea poisoning,” Am. J. Med. 69: 167–169 (1980).

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