Drug Synergy – Mechanisms and Methods of Analysis

The term synergy is derived from the Greek syn-ergos, "working together". Synergies have been described in many settings and situations of life, including mechanics, technical systems, human social life, and many more. In all cases, synergy describes the fact that a system, i.e. the combination and interaction of two or more agents or forces is such that the combined effect is greater than the sum of their individual effects. This definition implies that there are three possible ways of such an “interaction of agents or forces”: these forces could simply add up, not affecting each other (no interaction), their combination could produce a greater than expected result (synergy), or the combination could lead to a result that is less than the sum of the individual effects. This “negative” summation is called antagonism. Interactions of biologically active agents are an important aspect of pharmacology and biomedicine. In this context, interaction describes the biological activity that results from the presence of several drugs at the same time. Such situations occur in numerous clinical situations: combinations of cytotoxic drugs in the treatment of cancer and infections require lower doses of each drug to obtain better therapeutic effects with less side-effect toxicity. combinations of antibiotics likewise combine better efficiency with fewer side effects and reduced development of resistance. many serious clinical situations require administration of several drugs simply because of multiple therapeutic indications. Although in such a case drug combinations are not formulated to look for synergies, the interactions of these drugs need to be assessed. the effect of one drug may be augmented by another drug that does not produce such an effect on its own In all these cases, multiple drugs are administered, and will show some form of interaction, synergistic, antagonistic, or none. Methods to determine and quantify drug interactions are thus an essential tool in pharmacology. Historically, extracts from plants, animals, or even soils were the first classified pharmaceuticals. These were complex mixtures rather than single agents, and some ingredients may have interacted with others. Over the years of development of pharmacy, isolation, synthesis and marketing of single drugs became the accepted standard. Whether a complex mixture or a combination of drugs is used, the biological interaction of all active substances should be known. Synergy may be observed in simple systems – two drugs that only act on one target protein can show synergism. In such a case we can study the interaction of the drugs mechanistically and determine why and