Muscarinic receptor blockade with oxybutynin reduces spontaneous and induced uterine muscle contractions

The uterus and the bladder have striking physiologic and anatomic similarities. Anticholinergic medications are commonly used to treat "overactive bladder" by targeting M2 and M3 muscarinic receptors. The uterus also contains M2 and M3 muscarinic receptors; however, current management of preterm labor does not target these receptors. We assessed whether muscarinic blockade with oxybutynin reduces both spontaneous and oxytocin-induced uterine muscle contractions.

Longitudinal strips of uterine tissue from pregnant rats (17-19 days gestation) were mounted on an isometric test apparatus to directly measure uterine muscle contractions. The effect of cumulatively higher concentrations of oxybutynin (100 nM to 100 uM) on both spontaneous and on oxytocin-induced (1 nM) uterine muscle contractility was tested.  We measured both the area under the curve (AUC) and the frequency of the uterine muscle contractions compared to water vehicle control. Measurements are presented as a percentage of baseline. Two-Way ANOVA with Dunnett's post hoc test was performed.

Uterine muscle strips harvested from pregnant rats consistently showed spontaneous muscle contractions. Oxybutynin resulted in a statistically significant decrease in both spontaneous uterine muscle strength (AUC) and contraction frequency compared to vehicle controls at concentrations ≥10 µM.  Oxytocin-induced uterine muscle contractions were also affected by oxybutynin. At concentrations ≥10 µM, uterine muscle strength (AUC) was reduced (p < 0.01), but no difference was observed in contraction frequency compared to controls.

Oxybutynin significantly reduces spontaneous uterine muscle contraction strength (AUC) and contraction frequency in our animal ex vivo model. It reduces oxytocin-induced uterine muscle contraction strength (AUC) but not contraction frequency. Antimuscarinic agents warrant future clinical investigation and may represent a novel treatment of preterm labor and "overactive uterus."