Synergistic relaxing effect of the paracetamol and pyrilamine combination in isolated human myometrium

ObjectiveTo evaluate the interaction type of the human uterine relaxant effect of the paracetamol-pyrilamine combination (PPC) in vitro.Study designUterine strips were contracted with KCl (60 mM) and treated with vehicle or increasing concentrations of paracetamol (1003200 ?M), pyrilamine (3.2100 ?M) or the PPC. The relaxing effects of the drugs alone and in combination were measured. Isobolographic analysis was used to determine the pharmacologic interaction type.ResultsParacetamol, pyrilamine and the PPC produced a significant relaxing effect on non-pregnant human uterine strips pre-contracted with KCl (60 mM). The EC30 values for paracetamol and pyrilamine on the uterine contraction were 2391.3 595.3 ?M and 14.7 1.7 ?M, respectively. The derived experimental EC30 for the PPC was 401.8 129.8 ?M. This value was significantly lower (p < 0.05) than the theoretical EC30 expected for a purely additive interaction, which was 1203.0 297.7 ?M for the PPC. The interaction index (?) was 0.33 0.14 for PPC, being statistically different from unity.ConclusionData suggest that low doses of the PPC can interact synergistically and therefore this drug association may represent a therapeutic advantage for the clinical treatment of dysmenorreic pain.