Drug Interactions with Targets or Receptors

When presented to the target, drug molecules can elicit reactions to switch on or switch off certain biochemical reactions. The main drug targets in the human body can be classified into three categories  

Hydrophilic or water-soluble drugs do not cross membranes. They stay in the bloodstream for durations that are normally short, lasting on the order of seconds, and mediate responses of short duration. In contrast, hydrophobic drugs require carrier molecules for transport through the bloodstream. Hydro-phobic drugs remain in the bloodstream and can persist for hours and days, providing much longer effects. 

Allosteric binding occurs when two molecules bind to different sites on the target. When the two molecules are identical, it is termed homotropic interaction. If the molecules differ from each other, it is termed heterotropic interaction. Binding is competitive when two different ligand molecules compete for the same site. We discuss ligand binding further in Chapter 3. The specificity of ligand-receptor interaction is illustrated in Exhibit 2.9. 

Covalent bonds are strong bonds. Actual bonds are formed between the interacting molecules via the sharing of electrons. Hence, this type of interac- 

The enzyme prostaglandin H2 synthase-1 (PGHS-1) manufactures prostaglandin H2, which is converted to prostaglandin E2 and causes fever and inflammation. PGHS-1 contains two protein subunits with long channels. 

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DRUG DISCOVERY TARGETS AND RECEPTORS Drug Interactions with Targets or Receptors 30... 

Histamine is released from mast cells during inflammatory or allergic reactions. It then produces its typical response by interaction with specific histamine receptors, of which there are several types. Hi receptors are associated with inflammatory and allergic reactions, and H2 receptors are found in acid-secreting cells in the stomach. Drugs to target both of these types of receptor are widely used. 

Lack of selectivity (C). Despite appropriate dosing and normal sensitivity, undesired effects can occur because the drug does not specifically act on the targeted (diseased) tissue or organ. For instance, the anticholinergic atropine is bound only to acetylcholine receptors of the muscarinic type however, these are present in many different organs. Moreover, the neuroleptic chlorpromazine is able to interact with several different receptor types. Thus, its action is neither organ-specific nor receptor-specific. 

Targets for drag action are the sites where a drug interacts with part of a body cell or other body component. These include receptors in cell membranes or within the cell itself, ion channels and carrier proteins in cell membranes and enzymes in body fluids. 

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