Histamine in health and disease.
Histamine is a potent vasoactive agent, bronchial smooth muscle constrictor, and stimulant of nociceptive itch nerves. Activation of H1-receptors plays a central role in the immediate allergic reaction, but has less of an impact in chronic allergic disorders where inflammatory infiltrates, additional mediators such as LTC4/D4/E4 and cytokines, and structural remodeling occur. Histamine, through its H1-receptor-mediated activities, appears to be primarily a proinflammatory agent, yet it does have some homeostatic functions in gastric acid production (H2-receptors) and the central nervous system (predominantly H3-receptors) (97, 98). The realization that first-generation antihistamines often had mixed pharmacological properties (e.g., anticholinergic actions) and crossed the blood-brain barrier led to the development of the second-generation drugs, which are more selective for H1-receptors, have less access to the central nervous system, and, therefore, a more favorable benefit-to-risk ratio (therapeutic index). The potential for combined H1-H3-antagonists remains to be fully explored, but offers another exciting opportunity for this ever-expanding family of beneficial drugs.
Repka-Ramirez
M Susana
MS
Georgetown University, Washington, DC, USA.
Baraniuk
James N
JN
D000818:Animals; D001249:Asthma / Q000209:etiology; D003139:Common Cold / Q000209:etiology; D004730:Endothelium, Vascular / Q000166:cytology; D006632:Histamine / Q000502:physiology*; D006636:Histamine Release; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology; D007073:Immunoglobulin E / Q000276:immunology; D006255:Rhinitis, Allergic, Seasonal / Q000209:etiology; D014581:Urticaria / Q000209:etiology
D007073:Immunoglobulin E; D006632:Histamine