Agonist-antagonist interactions in the skin: comparison of effects of loratadine and cetirizine on skin vascular responses to prick tests with histamine and substance P.
The skin vascular responses (weal, flare, blood flow measurements) elicited by intradermal administration by pricking of histamine (HS) and substance P (SP) were evaluated 6 h after a single intake of anti-H1 agents displaying different activity profile on skin tests at currently recommended dosages (loratadine 10 mg, cetirizine 10 mg) as compared to placebo (P). The weal and flare response and the increases of blood flow occurring in the usual flare area after HS and SP were almost completely abolished by cetirizine. Inhibition of HS- and SP-induced weal and flare reactions was less marked after loratadine and blood flow in the expanding flare after HS and SP showed significant fluctuations over time. In view of the present results and of data obtained in previous experiments with intradermal injection of agonists, we hypothesize that mode of administration of agonists significantly influences the size of the residual weal after anti-H1 agents. We demonstrate that SP weals induced by pricking are largely inhibited by a potent H1 blockade which supports the view that this phenomenon, as well as the SP-flare, is due to SP-induced histamine liberation. We also, for the first time, report on fluctuations recorded at the edge of the developing flare with laser Doppler flowmetry early after prick testing with a weak H1 blockade. This opens up new avenues in dynamically testing H1-receptor occupancy in vivo and in situ in human skin.
Van Neste
D
D
Skin Study Center, Skinterface, Tournai, Belgium.
Coussement
C
C
Ghys
L
L
Rihoux
J P
JP
D000328:Adult; D001783:Blood Flow Velocity / Q000187:drug effects; D017332:Cetirizine / Q000494:pharmacology*; D005260:Female; D006632:Histamine / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D017336:Loratadine / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D012867:Skin / Q000098:blood supply / Q000187:drug effects* / Q000276:immunology; D012882:Skin Tests; D013373:Substance P / Q000494:pharmacology
D006634:Histamine H1 Antagonists; D013373:Substance P; D017336:Loratadine; D006632:Histamine; D017332:Cetirizine