In vitro effects of diazepam on human ciliary function.
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.
Johnston
M
M
Department of Otolaryngology, Queen Elizabeth Hospital, University Hospital Trust, Birmingham, England.
Watts
S
S
Drake-Lee
A
A
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
D015220:Calcium Channels; D003470:Culture Media; D018757:GABA Modulators; D003975:Diazepam