Histamine is a biogenic amine found in many tissues, including mast cells, basophils, lymphocytes, neurons, and gastric enterochromaffin-like cells. It is an autacoid, a molecule secreted locally to increase or decrease the activity of nearby cells. Histamine is a major mediator of allergic and inflammatory processes and also has significant roles in the regulation of gastric acid secretion, neurotransmission, and immune modulation1.
Physiology of Histamine
Histamine is synthesized from the amino acid L-histidine. The enzyme histidine decarboxylase catalyzes the decarboxylation of histidine to 2-(4-imidazolyl)ethylamine, commonly known as histamine. The synthesis of histamine occurs in mast cells and basophils of the immune system, enterochromaffin-like (ECL) cells in the gastric mucosa, and certain neurons in the central nervous system (CNS) that use histamine as a neurotransmitter1.
Histamine acts directly on the blood vessels to dilate arteries and capillaries; this action is mediated by both H1- and H2-receptors. Capillary dilatation may produce flushing of the face, a decrease in systemic blood pressure, and gastric gland secretion, causing an increased secretion of gastric juice with high acidity. Increased capillary permeability accompanies capillary dilatation, producing an outward passage of plasma protein and fluid into the extracellular spaces, an increase in lymph flow and protein content, and the formation of edema2.
Pharmacology of Antihistamines
Antihistamines are synthetic drugs that selectively counteract the pharmacological effects of histamine3. They are not receptor antagonists but are inverse agonists, i.e., they produce the opposite effect on the receptor to histamine4, 5. Antihistamines block histamine at H1 receptors, inhibit smooth muscle constriction in blood vessels and the respiratory and GI tracts, and decrease capillary permeability, salivation, and tear formation6.
First-generation antihistamines are less effective than second-generation antihistamines and have unwanted side effects, particularly central nervous system and anti-cholinergic effects. Second-generation antihistamines are more efficacious and safe for the treatment of allergic disease4. Of the three drugs highlighted in this review, levocetirizine and fexofenadine are the most efficacious in humans in vivo5. However, levocetirizine may cause somnolence in susceptible individuals, while fexofenadine has a relatively short duration of action, requiring twice-daily administration for full all-round daily protection. Desloratadine is less efficacious, but it has the advantages of rarely causing somnolence and having a long duration of action4, 5.
Histamine plays a crucial role in various physiological and pathological processes. Antihistamines, particularly second-generation ones, have proven to be effective in managing conditions where histamine plays a detrimental role. Understanding the pharmacology of histamine and antihistamines can lead to the development of more effective therapeutic strategies for conditions such as allergies and inflammatory diseases.