Inhibitory Effect of Loratadine and Clemastine on Histamine Release in Human Skin

Abstract

The inhibitory effect of the two H₁ antagonists clemastine and loratadine on histamine release in human skin was studied in 15 volunteers. The antihistamines and placebo were administered orally (clemastine 2 mg twice a day, loratadine 10 mg once a day) for 5 days according to a double-blind, crossover design. Clemastine caused a significant sedation in comparison with placebo, whereas there was no difference between loratadine and placebo in this respect. After 5 days’ medication, flare reaction was induced by intradermal injection of histamine and the histamine liberator compound 48/80. The antihistamine dosages were approximately equipotent and inhibited the flare response induced by histamine to about the same extent, whereas the flares induced by compound 48/80 were still more inhibited by both drugs. The results indicate that clemastine and loratadine not only inhibit histamine effects at H₁ receptor level, but have additional suppressive effects, probably due to inhibition of mast cell degranulation. The simple, virtually noninvasive, in vivo technique described in this paper does not require chemical analysis of the released mediators and could be used to screen ‘mast cell stabilizing’ effects of various antihistamines.

H1-antihistamines suppress wheal-and-flare reaction and skin blood perfusion measured by Laser Dopppler flowmetry: randomized, double-blind, placebo-controlled, crossover design study

“…The most prominent sedative effect, as found in other studies, was observed after intake of the first generation antihistamine clemastine (Frolund et al, 1990;Hagermark et al, 1992). Quifenadine and sequifenadine did not demonstrate any significant sedative effect compared to the placebo.…”

Use of induced cutaneous immediate‐type hypersensitivity reactions to evaluate anti‐inflammatory effects of triamcinolone topical solution in three dogs

“…It is also likely that the optimum injected substance with which to demonstrate such an eect may vary with the pharmacologic action of the drug under study; for example, under dierent circumstances, serial histamine injections may be ideal to demonstrate suppression of skin test reaction by a histamine H 1 -receptor antagonist. 6,9,10 Investigations using similar intradermal-test models are thus best performed using several injected substances to maximize the chances of observing an eect. Also of note was the sometimes-disparate comparison of the visible immediate reaction to the 24-h histological appearance.…”

“…Ideally, studies incorporate several of these techniques to assess multiple aspects of the cutaneous hypersensitivity response, including the immediate visible wheal-and-¯are reaction, early cellular in®ltrate in the so-called`late-phase reaction' (LPR), and later cellular in®ltrate associated with delayed-type hypersensitivity. These models have been used in humans 1,3±6,8,9,11 and in animals, 2,7,10,12,13 both to study mechanisms of in¯ammation 1,2,6,7 and to determine the eects of drugs on cutaneous in¯ammation. 3±5,8±12 Dogs have received comparatively little study in this regard, despite the clinical importance of veterinary topical and systemic medications that purport to reduce in¯ammation in the skin.…”

Anti‐inflammatory effects of low‐intensity extremely high‐frequency electromagnetic radiation: Frequency and power dependence

“…This release of histamine to blood flow causes the anti-inflammatory effects of EHF EMR manifested as inhibition of migration of leukocytes to the inflammatory focus and reduction of their functional activity, which were registered as decrease in exudative edema and hyperthermia of inflamed region. Low doses of clemastine, producing comparatively low concentrations of the drug in blood, dose-dependently inhibit the mast cell degranulation, presumably by the receptor-independent mechanism [Hagermark et al, 1992;Graziano et al, 2000;Assanasen and Naclerio, 2002]. These low doses of clemastine weakly influence the edema development at zymosan-induced inflammation [Erdo et al, 1993].…”