Selective Toxicity

Abstract

A drug can be considered toxic in that it replaces the natural ligand for a receptor. A goal in drug design is develop a molecule that is selective for a particular receptor located on a specific target organ or tissue. Therefore, an ideal biologically active molecule will produce a specific pharmacological response without causing adverse reactions. There are at least four ways to improve a drug's selectivity. These methodologies are based on the biochemistry of the disease or the biochemistry of the drug's receptor, unequal distribution of the drug, differences in the target cell's structure and the drug's stereochemical properties. Pharmacological classes differ in their ability to show selectivity. Cancer chemotherapeutic agents generally show poor selectivity whereas phosphodiesterase inhibitors can be selective for a specific enzyme isoform. Most bacterial antibiotics show excellent selective toxicity for bacteria with minimal serious adverse reactions experienced by the patient. In contrast, antiviral and antifungal drugs can produce untoward reactions in patients. Monoclonal antibodies exhibit excellent antigen–antibody specificity, but can disrupt the normal immune response. The nonsedating antihistamines distribute less to the central nervous system relative to the first generation of antihistamines. The initially inactive proton pump inhibitors readily distribute to an extracellular space with high acidity that converts them to the active drug. To improve patient acceptance, an important goal is to design the drug such that it be transported to the desired receptor and ignore other sites.

Introducing tox‐Profiles of Chemical Reactions

“…Then otion of selective action suggests that agiven substance manifests high specific biological activity against al imited number of targets,w hile being generally harmful otherwise. [15] Although ad etailed Figure 1. Functional groups have an impact on biologicala ctivity.A s seen by the example of benzene and its derivatives, introduction of asimple functionalg roup can significantly affect the toxicity of the compound.…”