title: The effect of oral zindotrine (MDL-257), a bronchial smooth muscle relaxant, on histamine airways responsiveness in asymptomatic asthmatics.
abstract: We evaluated the efficacy of an oral dosage form of the investigational smooth muscle relaxant, zindotrine, a novel pyridazine derivative, in counteracting histamine-induced bronchospasm in a group of 12 non-medicated asymptomatic asthmatics. Histamine inhalation challenges were performed before (control) and 45, 150, and 300 minutes after zindotrine (200 and 300 mg), or the corresponding dose of placebo was administered orally in a randomized, double-blind crossover fashion. When compared to the control state, the 300-mg zindotrine dose markedly lowered histamine airway responsiveness as indicated by a significant (P less than .01) increase in the inhaled histamine dose necessary to provoke a 20% decrease in the forced expired volume in one second (PD20FEV1) 45 minutes after drug administration. The PD20FEV1 then decreased linearly over time but remained higher than the control PD20FEV1 value (P less than .05) during the entire observation period. The 200-mg zindotrine dose failed to affect the PD20FEV1. Our data indicate that orally administered zindotrine lowers airways responsiveness to inhaled histamine in asymptomatic asthmatics in a dose-dependent and time-dependent fashion.
authors.forename: M
authors.initials: M
authors.lastname: Küng
authors.forename: S E
authors.initials: SE
authors.lastname: Bangs
authors.forename: E E
authors.initials: EE
authors.lastname: Gordon
authors.forename: K B
authors.initials: KB
authors.lastname: Barker
authors.forename: L
authors.initials: L
authors.lastname: Diamond
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy*; D001985:Bronchial Provocation Tests; D001986:Bronchial Spasm / Q000517:prevention & control; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004311:Double-Blind Method; D006632:Histamine; D006801:Humans; D008297:Male; D011724:Pyridazines / Q000627:therapeutic use*; D011897:Random Allocation
chemical_list: D001993:Bronchodilator Agents; D011724:Pyridazines; D006632:Histamine; C053632:zindotrine