Lastly, all HIt is now more than a century since the discovery of histamine, more than 70 years since the pioneering studies of Anne Marie Staub and Daniel Bovet led to the discovery of the first antihistamine and more than 60 years since the introduction into the clinic of antergan in 1942, followed by diphenhydramine in 1945 and chlorpheniramine, brompheniramine, and promethazine later the same decade.
Medicinal chemistry was very different in those days compared with the present day as elegantly described by Emanuel in his review entitled "Histamine and the antiallergic antihistamines: a history of their discoveries." The usual way of testing novel compounds was to measure histamine-induced contractions of pieces of muscle from experimental animals, usually guinea-pig intestine, suspended in an organ bath.
Second, they have unwanted side effects, particularly central nervous system and anti-cholinergic effects, and have the potential for causing severe toxic reactions which are not shared by second-generation H-antihistamines on the market for the treatment of allergic disease.
Of the three drugs highlighted in this review, levocetirizine and fexofenadine are the most efficacious in humans in vivo.
During this time, knowledge of the nature and diversity of receptors was rudimentary to say the least and it was only several decades later that the existence of more than one species of histamine receptor was discovered.
This review will concentrate on the histamine H-receptor is a member of the superfamily of G-protein coupled receptors.
C, A surface view of an inactive receptor with cetirizine linking domains IV and VI.-receptor, like other G-protein coupled receptors, may be viewed as "cellular switches," which exist as an equilibrium between the inactive or "off" state and the active or "on" state.
In the case of the histamine H-receptor, histamine cross-links sites on transmembrane domains III and V to stabilize the receptor in its active conformation, thus causing the equilibrium to swing to the on position (Figure 1B).
In the United States, reports of serious and often life-threatening adverse events of promethazine in children led to a "boxed warning" being added in 2004 to the labeling of promethazine.
The warning included a contraindication for use in children younger than 2 years and a strengthened warning with regard to use in children 2 years of age or older.
Histamine stimulates the receptor after its penetration into the central core of the receptor.