Potentiation and Synergism

These terms have been used and defined variously but, nevertheless, they refer to the toxicity of combined pollutants as being greater than would be expected from the toxicities of the compounds administered separately. It is 

Synergistic Effect of Ozone and Sulfur Dioxide on Tobacco Bel W3 Plants 

The terms synergism and potentiation have been variously used and defined but, in any case, involve a toxicity that is greater when two compounds are given simultaneously or sequentially than would be expected from a consideration of the individual toxicities of the compounds. 

Although examples are known in which synergistic interactions take place at the receptor site, the majority of such interactions appear to involve the inhibition of xenobiotic-metabolizing enzymes. Two examples involve the insecticide synergists, particularly the methylenedioxyphenyl synergists, and the potentiation of the insecticide malathion by a large number of other organophosphate compounds. 

The best-known example of potentiation involving insecticides and an enzyme other than the monooxygenase system is the increase in the toxicity of malathion to mammals brought about by certain other organophosphates. Malathion has a low 

Synergistic action is often seen with drugs. Almost all cases of increased hexo-barbital sleeping time or zoxazolamine paralysis time by other chemicals could be described as synergism or potentiation. Synergism may also result from competition for binding sites on plasma proteins or for the active secretion mechanism in the renal tubule. 

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It should be noted that synergism and potentiation may be defined in the reverse way in some texts, and the term insecticide synergists," as defined here, usually reflects potentiation. The definition used here is the same as that used in pharmacology. 

The terms synergism and potentiation have been used to indicate the enhanced toxicity obtained by mixing two compounds. However, it is generally accepted that in the case of synergism, one compound is nontoxic when administered alone, as described earlier, whereas in the case of potentiation, both compounds are toxic when administered alone. 

Synergism refers to a greater toxic response with exposure to two chemicals than would be expected based on the toxic response elicited by either of the chemicals alone. Potentiation is similar to synergism in that greater toxicity is seen with exposure to two chemicals than expected based on the responses elicited by those chemicals alone, but in this case one of the chemicals has no capacity to elicit the toxic response on its own. Using the toxicity grading scale above, examples of synergism and potentiation can be considered. 

Interactions between substances are expressed in terms of synergism, potentiation and antagonism, sometimes with more than additive and less than additive effects. The terms synergism and potentiation are often used to express the same type of phenomenon, a more than additive effect. Sometimes, however, the term synergism is restricted to the case where one of the compounds has no influence on the toxic effect under study at actual exposure level but strongly enhances the effect of the other in the combined exposure situation. Potentiation is then restricted to describing effects where two or more compounds each contribute to an overall toxicity that is more than additive. 

Hewlett (l%8) distinguished between synergism and potentiation, saying (hat if one compound is toxic on its own, and that another on its own is not , then if a combination of the two is more toxic than the insecticidal component alone, synergism will be said to occur. Whereas if two compounds are each separately toxic to the insect, and if the toxicity of the combination is greater than expected from the sum of the toxicities of (he separate components, potentiation will he said to have taken place. ... 

Schinazi RF (1991) Combined therapeutic modalities for viral infections - rationale and clinical potential. In Chou TC, Rideout DC (eds) Synergism and antagonism in chemotherapy. Academic, Orlando, FL, pp 110-181... 

In the following, several terms used to describe interactions between chemicals are mentioned as well as basic concepts used in the hazard and risk assessment of chemical mixmres. The description of these basic concepts, first outlined by Bliss (1939) and Placket and Hewlett (1952), are based on the publications by Konemann and Pieters (1996), Cassee et al. (1998), and Groten et al. (2001). The definitions of additivity, synergism, antagonism, and potentiation are those of Klaassen (1995) and Seed et al. (1995). 

Synergism - a potentiation or prolongation which results in much greater than expected effects. This could involve competitive substrates for an enzyme or receptor, decreased excretion, displaced plasma protein binding, etc. The analgesic propoxyphene (Darvon ) slows down the excretion of ethanol and so increases the depressant effects of the alcohol. Recall the example given earlier of the monoamine oxidase inhibitors used as antidepressants and the tyramine-containing foods which could precipitate a hypertensive crisis. 

Dispositional interactions are those in which one chemical affects the disposition of the other, usually metabolism. Thus, one chemical may increase or inhibit the metabolism of another to change its toxicity. For example, 2,3-methylenedioxynaphthalene inhibits cytochrome P-450 and so markedly increases the toxicity of the insecticide carbaryl to flies (potentiation) (see chap. 5). Another example, which results in synergy, is the increased toxicity of the organophosphorus insecticide malathion (see chap. 5) when in combination with another organophosphorus insecticide, EPN. EPN blocks the detoxication of malathion. Many chemicals are either enzyme inhibitors or inducers and so can increase or decrease the toxicity of other chemicals either by synergism or potentiation (see chap. 5). 

If V < 0.7, there is antagonism if V = 0.7 - 1.3, an additive effect occurs if V = 1.3 - 1.8, the effect is more than additive if V > 1.8, there is synergism or potentiation. For further discussion, see Brown (4) and references therein. Note that these interactive effects may occur with single acute doses or repeat dosing, and may depend on the timing of the doses relative to each other. 

The possibilities for synergism, antagonism, and potentiation among chemicals, the allergic type responses, and the impaired detoxification and excretion mechanisms in substantial groups of people all call for less... 

The chemistry of heteronuclear cluster compounds is significantly less developed than that of homonuclear clusters. Since 1980, rational synthetic methods [1] and effective characterizational techniques have been developed [2-6], Much of the interest provoked by these molecules stems from the fact that they have interesting chemical properties and potentially unique catalytic properties arising from the synergic effects of polar metal-metal bonds [6]. 

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