Action general chemical structure

An alternative nomenclature (Type I and Type II) has been proposed for subgroups of pyrethroids based not only on the syndromes of intoxication produced in mammals but also on their chemical structures, their signs of poisoning in insects, and their actions on insect nerve preparations [2, 14, 18]. The Type I/II nomenclature has been used in parallel with the T/CS nomenclature, so that Type I and Type II pyrethroids are generally considered to induce T- or CS syndrome, respectively [4]. However, the relationship between the two syndromes and types are neither necessarily confirmed in all pyrethroids nor absolute from the recent available data. 

Having considered the general relationships of chemical structure with these four different pharmacological actions, might we first look in detail at six compounds whose clinical... 

The connection between chemical structure and biological action of corticosteroids is extremely complex. However, it is possible to make a number of generalizations. 

Herbicides, used to kill or damage a plant, are the most rapidly growing segment of pesticides. Prior to the 1930s, herbicides were non-specific and often very toxic to humans as well as other animals. In the 1930s, in parallel with the development of new insecticides, researchers discovered several chemicals that selectively killed plants. These chemicals are now widely used to increase food production and have been used in warfare. Herbicides come in a variety of chemical structures and mechanisms of action, so they will be discussed in only general terms. Interested readers are referred to the many web sites and extensive literature on herbicides (see below and the presentation). 

Because of multiple receptor actions, which occur at different concentrations, different neuroleptics have different action profiles. There are many classifications for neuroleptic drugs, the least useful of which is probably based on their chemical structure. Other classifications include linear classifications based on the propensity to cause EPS, or multidimensional ones such as the Liege star which combines information on three positive effects (anti-autistic, antiproductive, antipsychotic), and three negative (hypotensive, extrapyramidal, sedative). In a general way, the more sedative neuroleptics such as levomepromazine, used more to treat acute agitation states, cause more hypotension related to alpha blockade, whereas those that act best on delirium (productive states) such as haloperidol tend to cause more EPS. 

Compounds that possess as their primary action the stimulation of the CNS can be divided into three major categories (Table 29.1) based on either their proposed mechanism of action or their chemical structure. Each class of compounds is discussed in general terms, and individual drugs are mentioned only as appropriate. 

It seems imreasonable to assume that any one of these theories alone accoimts for the toxic effect of oils on stages other than the egg. It is more likely that several operate simultaneously and that other modes of action are also involved. In generalizing, it would appear that the chemically active unsaturated oils might exert a toxic effect by virtue of their chemical structure. However, the highly refined saturated petroleum oils being less reactive would appear to exert their toxic effect chiefly through their physical characteristics. 

It is very rare that a single chemical structure will produce all the lour primary actions of a demulsifier, namely. (I) strong interface attraction. (2) flocculation. (3) coalescence, and (4) solids wetting. Generally two or more structures are blended to gethcr to produce a compound which gives the necessary combination ol actions. 

It was at the turn of the twentieth century that the importance of lipid solubility in drug action was also independently described by Meyer and Overton (the significance of the oil/water partition coefficient was discussed in Chapter 2). The importance of lipid solubility in drug action subsequently became manifested in the lipoid theory of cellular depression. In essence, this theory correlated a pharmacological effect (e.g., CNS depression) with a physical property (i.e., lipid solubility) rather than a structure-activity relationship. In the process, the theory was attempting to explain the diverse chemical structures that exist within the hypnotic and general anesthetic classes of drugs (see Chapter 11). Today, we realize the limitations of the lipoid theory and appreciate that the distinction between physical and chemical factors is illusory, since chemical structure is a determinant of physical properties. 

Drag metabolism involves the alteration of the chemical structure of the chug by an enzyme. It generally involves the transformation of a lipid-soluble drag (which can cross membranes and thus reach its site of action) into a more polar, water-soluble compound which can be rapidly eliminated in the urine. 

Quantitative Structure Activity Relationship (QSAR) is a method that makes predictions by the quantitative description of molecular properties with the use of descriptors of the chemical structure (Dearden 2003). This means QSAR models describe the quantitative or calculated relationship between a chemical structure and their biological activity (e.g. toxicity) with the help of chemical descriptors that are generated from the molecular structure (Durham and Pearl 2001). This relationship is described in from of a mathematical equation (e.g. log 1/C = a tt + b a +. .. + const). QSAR models generally show better predictivity if all compounds of a dataset involved in the prediction are derived from a congeneric series of compounds, that means they should all act by the same mechanism of action, since the physico-chemical and structural descriptors used in the QSAR reflect the same mechanism of action. Sometimes it is difficult to determine the mechanism of action, so series of compounds involved in a QSAR model are often restricted to a given chemical class in the hope that this will ensure a single mechanism of action (Dearden 2003). 

General theories concerning the relation between chemical structure and physiopathological action have been elaborated with especial reference to the war gases. From among the many published, an account is given here of two Meyer s Theory and the Toxophor-Auxotox Theory. 

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