Pharmacological Modulation by Cetirizine and Atropine of the Histamine- and Methacholine-Induced Wheals and Flares in Human Skin

Abstract

This study was planned to verify whether different methods for the measurement of skin reactivity, i.e. wheal and flare area, wheal thickness, skin capacitance and transepidermal water loss, were or were not able to discriminate between intradermally injected agonists (histamine and methacholine). For evaluating agonist/antagonist interactions, we adopted a cross-over, double-blind, placebo-controlled study designed to compare the effects of cetirizine and atropine. The intradermal injection of agonists elicited the appearance of wheal and flare reactions and, after histamine, the skinfold thickness was significantly increased. Skin capacitance and transepidermal water loss measurements reflected sweat gland activation after methacholine injection but were, respectively, not or less affected by histamine dry skin prick test or saline; hence, both methods appear very sensitive for in vivo testing of cholinomimetic agents. Cetirizine inhibited all the specific skin modifications induced by histamine challenge, wheals, flares and increased thickness, without affecting the methacholine-induced perspiration. This would further support the H1 specificity of this anti-H1 agent in vivo. However, at the agonist/antagonist ratios tested in view of the safety of the test persons, we were unable to objectivate methacholine blockade by atropine.

Methacholine induces wheal‐and‐flare reactions in human skin but does not release histamine in vivo as assessed by the skin microdialysis technique

“…Upon intradermal injection of cholinergic agonists in man, wheal-and-flare reactions develop (7,8,12,29). We confirmed this observation with methacholine.…”

“…We confirmed this observation with methacholine. Cetirizine, a highly selective Hj-receptor antihistamine, was shown to block methacholineinduced skin reactions ((12), and J. P. Rihoux, personal communication), but conflicting results have been published (29). Atropine had no influence on the skin responses by methacholine in doses which caused systemic side-effects (29).…”

“…Cetirizine, a highly selective Hj-receptor antihistamine, was shown to block methacholineinduced skin reactions ((12), and J. P. Rihoux, personal communication), but conflicting results have been published (29). Atropine had no influence on the skin responses by methacholine in doses which caused systemic side-effects (29). The cholinergic agonist carbachol induced a flare reaction in human skin but did not release histamine from rat peritoneal mast cells (8).…”

“…Furthermore, nasal challenge with methacholine results in the release ofhistamine into the nasal cavity (9). Upon intradermal injection in man, methacholine elicits a wheal-and-flare reaction (7,12,29).…”