Histamine antigen-induced

Chloro-oxazolo[4,5-/i]quinoline-2-carboxylic acid methyl ester was the most active compound in tests for inhibitors of antigen-induced release of histamine in vitro from rat peritoneal mast cells (IC50 of 0.3 p,M) and as inhibitors of IgE-mediated passive cutaneous anaphylaxis in the rat (ED50 (intraperitoneal) of 0.1 mg/kg in dose 0.5 mg/kg as an inhibitor of the test)—10 times and 60 times more potent, respectively, than the disodium salt of cromoglycic acid (85JMC1255). 

The mast cell stabilizers currently for ophthalmic use are nedocromil and pemirolast. These drugp are used for the prevention of eye itching caused by allergic conjunctivitis. The mast cell stabilizers act by inhibiting the antigen-induced release of inflammatory mediators (eg, histamine) from human mast cells. 

Intranasal anticholinergic agents (e.g., ipratropium) reduce the severity and duration of rhinorrhea but have no effect on other nasal symptoms.11,12,21 Ipratropium reduces cholinergic hyperreactivity and cholinergically mediated histamine- and antigen-induced secretion. Intranasal ipratropium acts locally, with only minimal systemic absorption. Clinical trials demonstrated that ipratropium bromide 0.3% reduced rhinorrhea in adults and children with PAR.11,12 Intranasal ipratropium is an option for patients in whom rhinorrhea is refractory to topical intranasal corticosteroids and/or antihistamines.8,12 Intranasal ipratropium is available only by prescription, and the dose is two sprays nasally two to three times daily.15 Adverse effects are minimal, but dry nasal membranes have been reported.11,12... 

Fexofenadine inhibited antigen-induced bronchospasm and histamine release from mast cells. No anticholinergic or alpha adrenergic-receptor blocking effects were observed. Moreover, no sedative or other CNS effects were observed. Fexofenadine does not cross the blood-brain barrier. It inhibits skin wheal and flare responses produced by histamine injection. Following single and twice daily oral administration, antihistaminic effects occurred within 1 hour, achieved a maximum at 2-3 hours, and lasted a minimum of 12 hours. 

The bronchodilation produced by the methylxanthines is the major therapeutic action in asthma. Tolerance does not develop, but adverse effects, especially in the central nervous system, may limit the dose (see below). In addition to their effect on airway smooth muscle, these agents—in sufficient concentration—inhibit antigen-induced release of histamine from lung tissue their effect on mucociliary transport is unknown. 

Flavonoids can affect the function of plasma membrane transport Na+- and K+-ATPase, mitochondrial ATPase, and Ca2+-ATPase. The Mg2+-ectoATPase of human leukocytes is inhibited by quercetin, which acts as a competitor of ATP binding to the enzyme. The sarcoplasmic reticulum Ca2+-ATPase of muscle is effectively inhibited by several flavonoids that were also active inhibitors of antigen-induced mast cell histamine release. 

Pearce, F. L., Befus, A. D., and Bienenstock, J. Mucosal mast cells. III. Effect of quercetin and other flavonoids on antigen-induced histamine secretion from rat intestinal mast cells. J Allergy Clin Immunol, 73(6), 819-823, 1984. 

Barbaro JF, Zvaifla NX Antigen induced histamine release from platelets of rabbits producing hnnologous PCA antibody. Proc Soc Exp Biol (N.Y.) 1966 122 1245-1247... 

Michel L, De Vos C, Rihoux JP, Burtin C, Benveniste J, Dubertret L. Inhibitory effect of oral cetirizine on in vivo antigen-induced histamine and PAF-acether release and eosinophil recruitment in human skin. J Allergy Clin Immunol 1988 82(l) 101-9. 

Cromoglicate inhibits mast-ceU degranulation and histamine release induced by phosphohpase A2, but does not interfere with the interaction of antigen and reaginic antibodies. Evidence is accumulating that it has an important stabilizing action on leukocytes, apart from mast cells, such as neutrophils, eosinophils, and monocytes, and that it also affects nerve reflexes in the lung (2). 

The anti-inflammatory and antiallergic effects of aromoline were evaluated via the measurement of antigen-induced histamine release from leukocytes, and it was found that the alkaloid inhibited antigen-induced histamine release [180]. 

Inhibition of PDE IV contributed to relaxation of airway smooth muscle and the prevention of proinflammatory cell activation. However, important side effects limited their therapeutic effects. In order to obtain new data on lignans as PDE inhibitors, Iwasaki et al. [204] synthesised a series of 1-aryl-2,3-bis(hydroxymethyl)naphthalene lignans and evaluated their ability to selectively inhibit PDE IV isolated from guinea pig and the histamine-induced and antigen-induced bronchoconstriction in the guinea pig. The more potent and selective compounds were the N-alkylpyridone derivatives (ring at C-l), and the most potent of these was 6,7-diethoxy-2,3-bis... 

A number of new orally active MRI s have been described. The oxamic acid (22) (PRH-836-EA) has an ED of 0.6 mg/kg p.o. in the rat PCA assayJ °The quinazoline carboxylate V23) was orally active (ED-q = 0.05 mg/kg) against anaphylactic bronchospasm in passively sensitized rats and inhibited the antigen-induced histamine release from passively... 

The bronchodilatory activity of khellin, a chromone obtained from a plant source Ammi visnaga) used by ancient Egyptians for spasmolytic activity, stimulated the search for related compounds with similar pharmaoological properties (14). From a study of many bischromones, cromolyn sodium was developed and marketed (Fig. 37.5). Although it prevents bronchospasm, it does not reverse antigen-induced bronchiolar constriction. Thus, it and other agents like it that followed prevent the release of histamine and do not block the effects of histamine at its reoeptors. 

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