Antiasthma activity of the novel antihistamine E-4716 in guinea pigs in vivo.
The effects of E-4716, a novel antihistamine compound, on histamine-induced bronchoconstriction, platelet activating factor (PAF)- or antigen-induced airway hyperreactivity, eosinophil infiltration, and airway microvascular leakage were compared with those of reference drugs in guinea pigs in vivo. E-4716 (300 microg/kg, i.v. or i.p.) suppressed histamine-induced bronchoconstriction in nonsensitized anesthetized guinea pigs and effectively inhibited acetylcholine-induced bronchial hyperreactivity in nonsensitized animals 24 h after PAF aerosol exposure. E-4716 also attenuated antigen-induced acute respiratory distress and suppressed histamine-induced airways hyperreactivity in conscious sensitized animals 24 h after antigen exposure, but did not affect the increased number of eosinophils in the bronchoalveolar lavage fluid. E-4716 300 microg/kg, i.v. or 1 mg/ml by inhalation (60 breaths) inhibited both PAF- and antigen-induced airway microvascular leakage. This in vivo profile of activity, comprising antihistamine, antihyperreactivity and antiexudative effects, suggests that E-4716 is of potential therapeutic value as an antiasthma and/or antiallergic drug.
Department of Pharmacology, Faculty of Medicine and Odontology, University of Valencia, Barcelona, Spain.
J
J
Cortijo
A J
AJ
Farré
B
B
Gutierrez
E J
EJ
Morcillo
D000704:Analysis of Variance; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001562:Benzimidazoles / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016084:Bronchoconstriction / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects*; D006168:Guinea Pigs; D006633:Histamine Antagonists / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000276:immunology; D008297:Male; D010972:Platelet Activating Factor / Q000008:administration & dosage / Q000494:pharmacology; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000503:physiopathology
D001562:Benzimidazoles; C104131:E 4716; D006633:Histamine Antagonists; D006634:Histamine H1 Antagonists; D010972:Platelet Activating Factor