title: Antiallergic effect of ZCR-2060: antihistaminic action.
abstract: 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.
authors.affiliation: Department of Pharmacology, Gifu Pharmaceutical University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Abe
authors.forename: T
authors.initials: T
authors.lastname: Omata
authors.forename: K
authors.initials: K
authors.lastname: Yoshida
authors.forename: T
authors.initials: T
authors.lastname: Matsumura
authors.forename: Y
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Y
authors.initials: Y
authors.lastname: Segawa
authors.forename: K
authors.initials: K
authors.lastname: Matsuda
authors.forename: H
authors.initials: H
authors.lastname: Nagai
mesh_terms: D000818:Animals; D001565:Benzoates / Q000009:adverse effects / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003877:Dermatitis, Contact / Q000517:prevention & control; D005106:Exploratory Behavior / Q000187:drug effects; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000009:adverse effects / Q000494:pharmacology*; D006967:Hypersensitivity / Q000188:drug therapy*; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D008815:Mice, Inbred Strains; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010880:Piperidines / Q000009:adverse effects / Q000494:pharmacology*; D011738:Pyrilamine / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012890:Sleep / Q000187:drug effects; D013874:Thiopental / Q000494:pharmacology
chemical_list: D001565:Benzoates; D006634:Histamine H1 Antagonists; D010880:Piperidines; C091433:ZCR 2060; D006632:Histamine; D011738:Pyrilamine; D013874:Thiopental