مرکز منطقه ای اطلاع رساني علوم و فناوري - اثرات مهاري كتوتيفن در مقايسه با تريوتالين ، دياراكسيد و ديكلوفناك بر روي انقباضات خودبخودي رحم در رات هوشيار

چكيده لاتين :

Ketotifen is a benzocycloheptathiophene with a range of pharmacological activities including inhibitory effect on rat isolated uterus contractions induced by KCI, acetylcholine or oxytocin. As the inhibition of contractile overactivity of the uterus is the base of the treatment of pre-term labor, provided that similar effect will be seen in vivo, then ketotifen may have clinical benefits for treatment of this condition. Therefore, the aim of this study was to investigate the inhibitory effect of ketotifen and diazoxide on uterus contractions in conscious rats, in comparison with 32 adrenoceptor agonist, terbutaline, ,and inhibitor of synthesis of prostaglandin (PG), diclofenac. For this purpose non-pregnant female Wistar rats (180-220 g) were anaesthetized with ketamine (75 mg/kg) and bilaterally ovariectomized. A micro-balloon was inserted into one of the uteri and a jugular vein was also eannulated. 24h later when rats were recovered from surgery and were freely feeding, drugs were delivered via jugular vein by an infusion pump and uterus contractions were recorded by connecting the micro-balloon tube to a pressure transducer. Blood pressure and heart rate were also assessed for same drug concentrations. Administration of terbutaline (400 µg/kg) had a quick inhibitory effect on uterus contraction and when infusion was completed (15 min) uterus contraction was reduced to 6±3% of the control value. This inhibitory effect persisted 2h after drug administration (36±15%). Diazoxide (45 mg/kg) also had an inhibitory effect on uterus contraction and at above times, contractions were reduced to 13±5% and 48±16% of the control values respectively. However, ketotifen even in high dose couldnʹt inhibit spontaneous uterus contraction in conscious rats and there was no significant differences between effect of saline and ketotifen (15 mg/kg). On the other hand, diclofenac (75 mg/kg) had a fine inhibitory effect on uterus contractions and at the end of the experiment, contraction was still 23±7% of the pre-drug administration value. Ketotifen and diclofenac did not affect the blood pressure significantly, but diazoxide at this concentration reduced blood pressure. The inhibitory effect of diclofenac suggest that synthesis and release of PG has an important role in spontaneous contractions of rat uterus in this method and it is possible that ketotifen is unable to inhibit contractions induced by PG. It can be concluded that this method is a suitable way to investigate effects of drugs on uterus contraction due to release of PG in vivo, and since PG have a major role in induction of pre-term labor, ketotifen is not a suitable drug for control of pre-term uterus contractions.