Magnesium sulphate (Mg) in vitro directly relaxes smooth muscle including myometrium. It is thought to compete with Ca thus, inhibit L-type Ca channel entry and contractility. Currently, the clinical evidence for using Mg as a tocolytic agent, such as for threatened preterm labour, is questionable: A Cochrane systematic review concluded that Mg for tocolysis in vivo is ineffective(1). We investigated whether the presence of the hormone oxytocin, which also effects calcium signalling dynamics, alters the tocolytic capability of Mg on human myometrium in vitro and if the effect (if any) could be reversed with the oxytocin antagonist, atosiban. Methods: Isometric tension recordings were performed on strips of myometrium (1x5x2mm) obtained from 10 pregnant women undergoing pre-labour Caesarean section (with consent and ethical approval). Paired strips from the same woman were superfused with physiological saline and the effect of increasing [Mg] from 1.2mM (control) to 12mM in the presence and absence of oxytocin (0.5nM) was compared by calculating the mean effective concentration causing 50% reduction in force amplitude of contraction (EC50). In a subset of experiments (n=4), the effect of increasing [Mg] in the presence of Atosiban (10-7M) on oxytocin-induced contractions was compared to Mg alone. Results: Elevated [Mg] produced a significant, dose-dependent inhibition of phasic, spontaneous myometrial contractions: EC50 2mM, complete inhibition achieved at 3.4mM. In contrast, application of oxytocin significantly increased the [Mg] required to affect contractions, such that at 2mM Mg there was little reduction in force amplitude (98.5% of control). The EC50 was 10mM and full abolition of activity in all but 2 cases was achieved at 12mM (i.e.10 times greater than [Mg] in control solution). The addition of Atosiban reduced the [Mg] at which oxytocin-induced contractions were inhibited, from 12mM to 6mM. Conclusion: In vitro, Mg at therapeutic doses (<2.5mM) significantly reduces spontaneous contractility of the myometrium however, the effect of Mg is significantly reduced in the presence of oxytocin; it is only effective at suprapharmacological concentrations. We suggest that the changed hormonal milieu in pregnancy, specifically towards oxytocin, underlies the poor tocolytic ability of Mg in vivo. Preliminary data suggest atosiban may reduce the EC50 for Mg and raises the question of whether, clinically, oxytocin antagonists should be used in combination with Mg for uterine tocolysis. [ABSTRACT FROM AUTHOR]