The different types of antihistamines.

H1 antihistamines are often prescribed to alleviate itching, sneezing, runny nose, and watery eyes. They work by blocking the H1 receptors of histamine, thereby inhibiting its effects on blood vessels and sensory nerves in the skin. H1 antihistamines are divided into two subcategories: first-generation antihistamines and second-generation antihistamines.

• First-generation H1 antihistamines.

  The first-generation H1 antihistamines such as diphenhydramine, chlorpheniramine, and hydroxyzine, are highly effective in treating severe itching and nausea, but their daily use is limited. Indeed, these drugs cross the blood-brain barrier and act on the central nervous system, causing significant sedative effects. That's why they are not recommended for elderly people and vehicle drivers.

• Second-generation H1 antihistamines.

  Second-generation H1 antihistamines are ideal for prolonged use, such as for seasonal allergies, as they cause fewer side effects. Their better tolerance is due to their lower affinity for the central nervous system. The antihistamines H1 of the second generation also constitute an interesting alternative when those of the first generation do not work. This group notably includes loratadine, cetirizine, and fexofenadine.

H2 antihistamines are primarily used to alleviate allergic reactions that manifest as gastrointestinal disorders, such as stomach and duodenal ulcers or gastroesophageal reflux. Among the most commonly used are ranitidine, famotidine, and cimetidine, which act specifically in the stomach by blocking the H2 receptors of the gastric parietal cells. These receptors, in connection with histamine stimulation, regulate the release of hydrochloric acid. This acid is normally secreted when histamine binds to the H2 receptors, which stimulates intracellular cAMP. By reducing gastric acidity, H2 antihistamines promote the healing of ulcers and prevent inflammation in the esophagus and stomach.

Still under development, for the treatment of narcolepsy and support of individuals with attention deficit disorder with or without hyperactivity (ADHD), H3 antihistamines could provide an alternative to traditional medications. They could also be beneficial in neurodegenerative disorders, such as Alzheimer's disease, which is notably characterized by a loss of histaminergic neurons.

In practical terms, H3 antihistamines work by blocking the H3 receptors in the central nervous system. This action increases the release of endogenous histamine, promoting alertness and wakefulness. Indeed, histamine plays a role in sleep-wake cycles, appetite regulation, and even energy management. H3 antihistamines inhibit the feedback mechanism that limits the release of histamine, indirectly stimulating the neurotransmission systems that maintain focus and alertness.

Currently under study, H4 antihistamines could limit inflammatory reactions by inhibiting the activation of H4 receptors. These receptors are primarily found in immune system cells, such as eosinophils, mast cells, and neutrophils. They play a central role in the inflammatory response and are activated in many allergic, autoimmune, and inflammatory reactions. Unlike corticosteroids, which broadly suppress the immune response, H4 antihistamines could offer targeted modulation, which could reduce the risk of superinfections.

H4 antihistamines are, among other things, being studied for chronic inflammatory diseases, such as asthma or atopic dermatitis, where inflammation is primarily caused by an overreaction of mast cells and eosinophils. They are also being explored as alternatives to non-steroidal anti-inflammatory drugs and corticosteroids because they could minimize side effects for long-term treatments.