The Dose-Dependent Effects of Duloxetine on the Mechanical Muscle Activities of Rat Diaphragms

ABSTRACT
Aim: Duloxetine is an active ingredient prescribed to patients for a wide range of conditions. Although the information with purchased drugs containing duloxetine mention various side effects on different muscle tissues, there is limited research available on the potential effects on the skeletal muscle of the diaphragm, which plays an important role in respiratory functions. In this study, the potential effects of different doses of duloxetine on in vitro mechanical activities of the diaphragm muscle were examined. Additionally, the impact of these activities on the diaphragm muscle was discussed in terms of the respiratory functions of patients prescribed duloxetine.
Materials and Methods: Sixteen adult Wistar-Albino rats, each 24 weeks old, were randomly divided into two groups: duloxetine(DLXT ) and vehicle( VHC). Diaphragm muscles were isolated from rats in both groups under anesthesia and transferred to a 5mL volume isolated organ bath, in which muscle strips were adjusted to a 2g preload. For DLXT group, the diaphragm muscles were cumulatively treated with duloxetine at concentrations of 1, 10, 20, 30, and 40 µg/mL, while VHC group received the same volume of the vehicle. Contractions were induced using square pulses of 0.5 Hz frequency and 1 ms duration.
Results: From the contraction curves, data was obtained on contraction force(g.mg-1), contraction time(s), relaxation time(s), under area curve(g.mg-1.s), +dF/dtmax(g. mg-1·s-1), and -dF/dtmax(g.mg-1.s-1). In DLXT group, relaxation time, area under the curve, +dF/dtmax, and -dF/dtmax parameters showed significant differences compared to the VHC group with the application of 10 µg/mL duloxetine. Similar difference was observed in contraction force and contraction time with the application of 30 µg/mL duloxetine.
Conclusions: The effects of duloxetine on diaphragm muscle contraction parameters observed in this study suggest that duloxetine may adversely affect respiratory functions. It is therefore important that the respiratory functions in patients prescribed duloxetine be closely monitored.
Keywords: Antidepressants, diaphragm, duloxetine, isometric contraction, respiratory