The various types of antihistamines.

Available in the form of tablets, syrups, nasal sprays or even eye drops, antihistamines are medicines used to combat an allergy. When the body is exposed to a substance it cannot tolerate, the immune system responds by releasing histamine, a chemical mediator synthesised by basophil granulocytes and mast cells, which are part of the white blood cell family. The histamine then attaches to H1, H2, H3 or H4 receptors and triggers a cascade of biological reactions that vary depending on the type of receptor. These reactions can include sneezing, itching, hives or even gastric disturbances.

As their name suggests, antihistamines halt the effects of histamines. These medications are used to alleviate allergies and the symptoms that accompany them.

H1 antihistamines are often prescribed to alleviate itching, sneezing, a 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.

  First-generation 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. This is why they are not recommended for elderly people and vehicle drivers.

• Second-generation H1 antihistamines.

  Second-generation H1 antihistamines are ideal for prolonged use, for instance in the case of 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 present an interesting alternative when the first-generation ones 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 oesophagus 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 characterised by a loss of histaminergic neurons.

In practical terms, H3 antihistamines function 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 and 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 are predominantly present 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 notably caused by an overreactivity of mast cells and eosinophils. They are also being explored as alternatives to non-steroidal anti-inflammatory drugs and corticosteroids as they could minimise side effects for long-term treatments.

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• PEARLMAN D. Antihistamines: pharmacology and clinical use. Drugs (1976).