Antiallergic effect of ZCR-2060: antihistaminic action.

The antihistaminic effect of 2-[2-[4-(diphenylmethyl)-1-piperadinyl]ethoxy] benzoic acid maleate (ZCR-2060), a newly synthesized antiallergic agent, was investigated in both in vitro and in vivo studies. ZCR-2060 clearly antagonized histamine-induced contraction of isolated guinea pig ileum and trachea. In contrast, carbachol-, BaCl2- and 5-hydroxytryptamine-induced contractions of isolated guinea pig ileum were slightly inhibited by higher concentrations of ZCR-2060. 3H-Mepyramine specific binding to membranes from guinea pig lung and brain were markedly inhibited by ZCR-2060 in a concentration-dependent fashion. In the in vitro studies, the antihistaminic effect of ZCR-2060 was greater than those of cetirizine and terfenadine, but was less than that of ketotifen. In the in vivo studies, ZCR-2060 significantly inhibited the histamine-induced cutaneous reaction in rats, when administered orally 1 hr before the histamine injection. Moreover, ZCR-2060 has a long-lasting antihistaminic effect. In the in vivo studies, the antihistaminic effect of ZCR-2060 was found to be greater than that of cetirizine and terfenadine, and it was the same as that of ketotifen. Thiopental-induced sleep and spontaneous ambulatory activity in mice, however, were unaffected by ZCR-2060 at higher doses. These results indicate that ZCR-2060 has a potent, selective and long acting histamine H1-receptor antagonistic action without causing any unwanted CNS side effect.