Inhibitory effects of histamine H1 receptor blocking drugs on metabolic activations of neutrophils.

Cysteinyl Leukotriene Production in Anaphylactic Reactions

“…The pathophysiological significance of increased histamine production in this patient is supported by the ob servation that pruritus and urticaria were mitigated by in travenous administration of an l lr receptor antagonist, dimethindene. However, this drug has considerable sedating side effects and may also affect leukotriene production as has been described with other H,-receptor blockers [21], En dogenous opioids probably did not play a major role in exer cise-induced anaphylaxis in this patient, because naloxone had no effect.…”

“…However, leukotriene inhibitors have been shown to be effective in the treatment of bronchial asthma in humans [17,18], and in the mitigation of several symptoms of anaphylaxis in animal models, in cluding coronary vasoconstriction [10], enhanced airway pressure and leukopenia [11], and anaphylaxis-induced le thality [8], Several basic pathophysiologic events observed in anaphylactic reactions, such as smooth muscle contrac tion and microvascular leakage, may be explained by the known actions of leukotrienes [19], Several agents commonly used for the treatment of ana phylaxis have been shown to possess the potential to inhibit leukotriene production. Epinephrine [20] and a number of H|-receptor blockers, including clemastine and azelastine [21], reduce leukotriene production by human leukocytes. Glucocorticoids may inhibit leukotriene production in some situations by blocking phospholipase A2 [22,23], thereby inhibiting the release of the leukotriene precursor fatty acid from membrane phospholipids.…”

Further studies on the mechanism of antiphagocyte-antioxidative effect of H1-antihistamines

“…Because the anti-infl ammatory effect of H 1 -antihistamines was assumed to result from the suppression of arachidonate pathway and inhibition of NADPH oxidase [7,8] we suggest that these compounds may act at intracellular level at different regulatory pathways. Intracellular interference of H 1 -antihistamines but not histamine, with the respiratory burst in neutrophils may help to explain their antiinfl ammatory activities plus indicates their usefulness in clinical situations.…”

Effect of H1-antagonist Dithiaden® on human PMN-leukocyte aggregation and chemiluminescence is stimulus-dependent

“…Second, Dit may act by inhibiting the arachidonic acid pathway of PMNL, which is closely related to the regulation of stimulated NADPH oxidase [34,38]. The inhibition of arachidonic acid liberation from human PMNL with different H 1 -antagonists was parallel with their inhibition of superoxide anion production [35]. In blood platelets, Dit like other CAD, inhibited dose-dependently the liberation of arachidonic acid from membrane phospholipids stimulated at different levels and inhibited thromboxane generation through stimulated human PMNL [11,26].…”

“…Moreover, different responses to His have been described in PMN-leukocytes stimulated with various stimuli to produce reactive oxygen species as measured directly (e. g. superoxide anion) or indirectly by luminolenhanced chemiluminescence methods [5,14,18,31]. Some H 1 -antagonists were reported to possess inhibitory effect on stimulated chemiluminescence, metabolic activation, degranulation, second messenger modulation, and to potentiate the inhibitory effect of histamine on PMN-leukocytes [2,21,35]. H 1 -antagonists recently characterised as inverse agonists or neutral antagonists stabilise the inactive conformation of the histamine receptor and may have inhibitory effects even in the absence of histamine [22].…”