Evolution, mechanism of action, and clinical applications of three generations of Antihistamines

Introduction. This review investigates the evolution, mechanisms of action, and clinical applications of three generations of antihistamines. Materials and methods: To identify relevant studies, an extensive search was performed across multiple databases, including PubMed, MEDLINE, Web of Science, and Scopus, using a strategic combination of keywords and MeSH terms. The selection process yielded relevant scientific literature sources published between 1985 and 2023. Results and discussion: the study demonstrated that the initial step in the creation and development of antihistamines involved analysing the mechanisms of anaphylaxis and allergy. This analysis led to the discovery of histamine as a mediator of allergic reactions and subsequently to the synthesis of substances with antihistamine effects, resulting in the gradual discovery of three generations of antihistamines. These drugs are designed to block H1-histamine receptors to eliminate allergic manifestations. Due to their non-selective antihistamine activity, first-generation drugs have many side effects, primarily sedation, in addition to their intended therapeutic effects. Second- and third-generation drugs are selective for peripheral H1 receptors and have significantly fewer side effects. The third generation of drugs, as active metabolites of the second generation, demonstrate the highest efficacy and safety profile. First-generation medicines are used for emergency care in acute allergic reactions and to reduce local allergy manifestations, whereas second and third generations are used to treat symptoms of seasonal and chronic allergic rhinitis. Conclusions: The significance of the study lies in the potential application of its results in the clinical practice of allergists.