The antiepileptic agents phenytoin and valproate inhibits oxytocin-induced contractions of myometrium isolated from absence epileptic WAG/Rij rats

Physiology 2019 (Aberdeen, UK) (2019) Proc Physiol Soc 43, C126

Oral Communications: The antiepileptic agents phenytoin and valproate inhibits oxytocin-induced contractions of myometrium isolated from absence epileptic WAG/Rij rats

A. Kurt1, A. K. Salihoglu1, A. Ayar1

1. Physiology, Karadeniz Technical University Faculty of Medicine, Trabzon, Turkey.

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There has been concern about safety of antiepileptic therapy during pregnancy including neurodevelopmental impairments in fetus, possible effects of antiepileptics on natural birth process is less clear. The aim of this study was to investigate possible effects of phenytoin and valproate on oxytocin-induced contractions of absence epileptic WAG/Rij rats. Myometrial strips were isolated from non-pregnant female rats and placed in an organ bath continually bubbled with oxygen and CO2, at 37 oC, pH 7.4. After equilibrium under 1 g of resting tension, contractions were stimulated by bath application of oxytocin and, effects of cumulatively applied phenytoin or valproate on area under the curve (AUC, normalized data) and frequency of contractions (number of contractions/10 min) were evaluated by 10-minute periods. Application of valproate caused a dose-dependent inhibition of AUC: 1±0; 0,94±0,1 (p>0.05), 0,82±0,1 (p<0.05), 0,61±0,18 (p<0.05) and 0,38±0,21 (p<0.05) oxytocin; 100, 300 uM, 1 and 3 mM valproate, respectively (n=9 for each dose). The frequency of oxytocin-induced contractions was 15,9±1,05 and reduced to 13,3 ±1,9, 11, 7±2,2, 9,6±3,0 and 6,3±4,3, after respective doses of valproate, (p<0.05, n=9, for all). Phenytoin also caused inhibition of AUC values oxytocin-induced contractions: 1±0; 0,87±0,08, 0,78±0,15, 0,33±0,21, oxytocin; 10, 30 uM and 1 mM, respectively (p<0.05 for all tested concentrations, n=8 for each). The effects of phenytoin on the mean frequency of oxytocin-induced contractions were significantly inhibited by all the tested concentrations. Although we tested higher concentrations of these agents, considering the increased antiepileptic drug clearance during pregnancy the need for higher doses may be relevant for the tested doses of these anti-epileptics and our findings may be of importance.



Where applicable, experiments conform with Society ethical requirements.

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