THE INTRADERMAL EFFECTS OF THE H-3 RECEPTOR AGONIST-R-ALPHA METHYLHISTAMINE IN HUMAN SKIN

We have investigated the possible existence of the H-3 histamine recep tor in human skin with the highly selective ligands R alpha methylhist amine (RAMHA) (H-3 agonist) and thioperamide (H-3 antagonist). We comp ared the intradermal effects of RAMHA with histamine, and studied thei r potential modulation by the H-1 antagonist terfenadine, and H-2 anta gonist cimetidine, The effects of RAMHA and thioperamide on codeine ph osphate-, substance P- and histamine-induced weal and flare responses were also studied. RAMHA produced dose-related weal and flare response s that were approximately 10- and fivefold less, respectively than res ponses to histamine, Flare responses to RAMHA were significantly inhib ited by oral terfenadine (P < 0.05). Weal and flare responses to hista mine after oral cimetidine showed much intersubject variation, and cim etidine did not significantly alter either RAMHA- or histamine-induced weal and flare responses. Codeine phosphate-, substance P- and histam ine-induced responses were not significantly affected by concurrent ad ministration of RAMHA, Thioperamide was not found to influence codeine phosphate-, substance P-, RAMHA- or histamine-induced effects. RAMHA induces vascular (weal and flare) responses in human skin, and these r esponses are partially inhibited by terfenadine, There is a trend for RAMHA to have an additive effect to the weal induced by substance P an d histamine, although our results largely do not reach statistical sig nificance. Thioperamide does not affect the vascular responses to RAMH A, codeine phosphate, histamine or substance P. We cannot conclude tha t the effects of RAMHA are induced by H-3 receptors on cutaneous endot helial or mast cells.