PRINCIPLES OF TOXICOLOGY - Biology East Borneo

432 PROPERTIES AND EFFECTS OF NATURAL TOXINS AND VENOMSment. Some of the toxins mentioned in this chapter are serving as molecular models for designingdrugs with novel mechanisms of action. For instance, the worm toxin anabaseine has been modifiedto eliminate its peripheral nicotinic agonist activity, and the resulting compound, DMXB-anabaseine(also known as GTS-21), is now undergoing human clinical tests as a possible Alzheimer’s drug (Kem,1995).The goal of drug development is to sever the connection between toxicity and therapeutic activityof compounds intended as drugs, but this ideal is rarely completely attainable. It is useful to keep inmind that the difference between toxin and drug is often a seemingly minor alteration of chemicalstructure, or at the least, proper selection of dosage. The sixteenth-century physician and chemistParacelsus understood the dual nature of Materia Medica when he stated that drugs are also poisons,and it is often a matter of dose whether the therapeutic or toxic effect predominates. For all the problemsthat natural toxins and venoms cause, our collective ability to use them as tools in biomedical researchand drug design makes them valuable reagents in medical research. Ultimately, these substances canbenefit, more than damage, human existence.17.9 SUMMARYA toxin is a single substance that adversely affects some biological process or organism, whereasa venom is a heterogeneous mixture of many substances, some of which are toxic. A poison iseither a single injurious substance or a mixture of substances and can be human-made (synthetic)or natural.Knowledge of the mechanism by which a toxin acts on some biological process provides theultimate basis for rational treatment of intoxication. While many protein intoxications are successfullytreated by immunotherapy, treatment of smaller nonpeptide toxins must be based upon pharmacologicantagonism as well as symptomatic treatment. It is extremely important to identify the toxin or venominvolved in an intoxication in order to select the appropriate treatment.Initial treatments, such as induction of vomiting, and gastric lavage, for orally ingested toxins andimmobilization of individuals bitten by poisonous snakes or other animals can reduce entry of thetoxin(s) into the systemic circulation, and thereby delay the onset and reduce the intensity of theresponse. Success often depends on the training of personnel responsible for initial care of the victim.While few human intoxications due to natural toxins or venoms are lethal when properly treated,delayed or inadequate treatment can be life-threatening.Toxins and venoms are not only potentially injurious to health but can also be beneficial in providingnew research tools for biomedical research and unique molecular models for designing new drugs.ACKNOWLEDGMENTSThe author thanks Barbara Seymour for artistic renderings of the poisonous organisms and Judy Adamsfor word-processing the manuscript.REFERENCES AND SUGGESTED READINGAmes, B., M. Profet, and L. S. Gold, “ Nature’s chemicals and synthetic chemicals: Comparative toxicology,” Proc.Natl. Acad. Sci. (USA) 87: 7782–7786 (1990).Anderson, D. M., “Red tides,” Sci. Am. 271: 62–70 (1994).Auddy, B., M. I. Alam, and A. Gomes, “ Pharmacological actions of the venom of the Indian catfish (Plotosus caniusHamilton),” Ind. J. Med. Res. 99: 47–51 (1994).Daly, J. W., “The chemistry of poisons in amphibian skin,” Proc. Natl. Acad. Sci. (USA) 92: 9–13 (1995).Dickstein, E. S., and F. W. Kunkel, “Foxglove tea poisoning,” Am. J. Med. 69: 167–169 (1980).