Studies on the uterine inhibitory actions of diphenylhydantoins

Diphenylhydantoin and diphenyl-thio-hydantoin inhibited the spontaneous motility of rat uterus in a dose-dependent manner. On molar basis diphenyl-thio-hydantoin was found to be 2.7 times as potent as diphenylhydantoin. The stimulant effects of acetylcholine, oxytocin, adenosine triphosphate, prostaglandins I2 and E2 were reduced by both hydantoins. Furthermore, hydantoins potentiated the inhibitory effects of sympathomimetic amines, theophylline, nitroglycerin and dibutyryl cyclic adenosine monophosphate. The uterine inhibitory actions of adrenaline, isoprenaline and phenylephrine were antagonized by propranolol but not by phentolamine. However, adrenergic blocking agents were ineffective against hydantoins indicating that their effects were not mediated through adrenergic receptors. Ouabain and sodium fluoride caused stimulation of uterine motility. Pre-treatment with ouabain did not block the inhibitory effect of hydantoins, while, sodium fluoride antagonized the inhibitory effects of hydantoins. Furthermore, even increasing the diphenylhydantoin concentration 10 times did not produce any relaxation in the presence of sodium fluoride. The results are discussed in relation to the effect of hydantoins on sodium pump and on membrane permeability.