title: In vitro effects of diazepam on human ciliary function.
abstract: This study demonstrated the in vitro effect of diazepam on human ciliary beat frequency (CBF) from fifteen normal subjects using brush cytology. Tube A contained culture medium, tube B the diluent that diazepam intravenous injectate was carried in and culture medium (controls). Tube C, D and E contained, 0.4 mg/l, 4.0 mg/l and 40.0 mg/l of diazepam in culture medium respectively. The mean effective diazepam concentration in plasma is 0.4 mg/l. CBF was measured photometrically. The most vigorous cilia were measured in 5 areas taking 10 readings on each sample, 30 minutes and 1 hour after mixing. Standard deviation (SD) and confidence limits were calculated along with significance testing (p < 0.05) using the paired t-test and ANOVA. The mean of the CBF of tubes A and B were 13.44 (SD 2.65) and 13.67 (SD 2.48). There was a reduction of the CBF with increasing concentrations of diazepam at 30 minutes, 11.32 (SD 2.14), 10.29 (SD 1.58) and 4.14 (SD 1.57) tubes C. D and E respectively. There was a significant lowering in CBF of 17% (p < 0.01) of diazepam at the mean effective plasma level (tube C) when compared against the controls. CBF decreased over time and at 1 hour was 10.57 (SD, 1.36), 9.02 (SD, 1.39) and 3.58 (SD, 1.31) tubes C, D and E respectively. A proposed mechanism of altered intracellular calcium flux via the action diazepam on GABA receptors is described.
authors.affiliation: Department of Otolaryngology, Queen Elizabeth Hospital, University Hospital Trust, Birmingham, England.
authors.forename: M
authors.initials: M
authors.lastname: Johnston
authors.forename: S
authors.initials: S
authors.lastname: Watts
authors.forename: A
authors.initials: A
authors.lastname: Drake-Lee
mesh_terms: D000328:Adult; D015220:Calcium Channels / Q000502:physiology; D002923:Cilia / Q000187:drug effects; D003470:Culture Media; D003975:Diazepam / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D018757:GABA Modulators / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009079:Mucociliary Clearance / Q000187:drug effects*; D009297:Nasal Mucosa / Q000187:drug effects / Q000648:ultrastructure; D013997:Time Factors
chemical_list: D015220:Calcium Channels; D003470:Culture Media; D018757:GABA Modulators; D003975:Diazepam