Antiallergic Effect of ZCR-2060: Antihistaminic Action

• Published in: Japanese journal of pharmacology 1994, Vol.66(1), pp.87-94
• Main Authors: Abe, Tooru, Omata, Takeshi, Yoshida, Kenji, Matsumura, Toshihiro, Ikeda, Yugo, Segawa, Yoshihide, Matsuda, Kazuo, Nagai, Hiroichi
• Format: Article
• Language: English
• Subjects: Animals; Antiallergic agent; Benzoates - adverse effects; Benzoates - pharmacology; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Dermatitis, Contact - prevention & control; Exploratory Behavior - drug effects; Guinea Pigs; Histamine - pharmacology; Histamine and antagonists. Allergy; Histamine H1 Antagonists - adverse effects; Histamine H1 Antagonists - pharmacology; Histamine H1-receptor antagonist; Hypersensitivity - drug therapy; In Vitro Techniques; Lung - drug effects; Lung - metabolism; Male; Medical sciences; Membranes - drug effects; Membranes - metabolism; Mice; Mice, Inbred ICR; Mice, Inbred Strains; Muscle Contraction - drug effects; Muscle, Smooth - drug effects; Non-sedative antihistamine; Pharmacology. Drug treatments; Piperidines - adverse effects; Piperidines - pharmacology; Pyrilamine - pharmacokinetics; Rats; Rats, Sprague-Dawley; Sleep - drug effects; Thiopental - pharmacology; ZCR-2060
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1254/jjp.66.87

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 Η1-receptor antagonistic action without causing any unwanted CNS side effect.