title: The protective effect of inhaled levomepromazine (Nozinan) on histamine-induced bronchial constriction.
abstract: The effect of inhaled levomepromazine (Nozinan, Veractil) on bronchial responsiveness to inhaled histamine was investigated in asthmatics. In a double blind, randomized controlled study, 12 asthmatics (FEV1% pred 52-96%, and PC20 histamine 1.01 mg/ml (geometric mean)) were challenged before and after inhalation of levomepromazine in three different doses. Before and after each inhalation of levomepromazine, PC20, FEV1, the continuous reaction time (CRT) and the subjective sedation score (VAS) were determined. A dose-dependent increase in PC20 was observed after inhalation of levomepromazine. PC20 was increased by up to 4.02 two-fold concentration differences (doubling), i.e. up to a 38-fold increase from the basic values. Inhalation of the two higher doses of levomepromazine had a small sedative effect evaluated from an increase in CRT and the VAS-score and corresponding to the plasma concentrations. We conclude that inhaled levomepromazine has a dose-dependent protective effect on histamine-induced bronchial hyperresponsiveness in asthmatics and that inhalation of levomepromazine was well tolerated. The mechanism by which levomepromazine acts on histamine-induced bronchial hyperresponsiveness is not known but it could be partly explained by the antihistaminic effect. In this respect levomepromazine bears comparison with the most potent second generation antihistamines. The plasma concentrations of levomepromazine measured corresponded to those seen after oral intake of 5-10 mg levomepromazine.
authors.affiliation: Department of Pulmonary Medicine Y, KAS Gentofte County Hospital, Hellerup, Denmark.
authors.forename: F
authors.initials: F
authors.lastname: Madsen
authors.forename: P
authors.initials: P
authors.lastname: Faurschou
authors.forename: A M
authors.initials: AM
authors.lastname: Banning
authors.forename: A M
authors.initials: AM
authors.lastname: Engel
authors.forename: P
authors.initials: P
authors.lastname: Sjøgren
authors.forename: A
authors.initials: A
authors.lastname: Rosetzsky
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D006632:Histamine; D006801:Humans; D008297:Male; D008728:Methotrimeprazine / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D008875:Middle Aged; D011930:Reaction Time
chemical_list: D006632:Histamine; D008728:Methotrimeprazine