ABSTRACT
The effect of diazepam on spontaneous uterine contractility was studied in-situ in both non-pregnant rats and pregnant rats at days 20 of gestation [GD20]. The effect of these drugs were given 15 minutes after injection of diazepam. The uterine response was identified in terms of frequency [number of bursts/10 minutes] and amplitude [micro V/10 minutes] of uterine contraction. Diazepam [0.25-4 mg/kg i.v.] showed significant [P < 0.05], dose-dependent tocolytic effect in both non-regnant and pregnant rats with greater effect in pregnant rats as reflected by greater reduction of both frequency and amplitude of uterine contraction. The dose of diazepam that produced 50% reduction in the amplitude of uterine contraction [ID50] in non-pregnant rats was 1.9 mg/kg compared to 0.4 mg/kg in pregnant rats. The ID50 ratio for diazepam in non-pregnant and pregnant rats was about 4.75. In both non-pregnant and pregnant rats, diazepam [1 mg/kg] markedly antagonized the uterotonic effects of oxytocin [1 IU/kg] and PGF2alfa was found to be greater on the muscles of pregnant rats. However, such antagonism did not result in complete loss of the uterotonic activity of oxytocin and PGF2alfa as their [after diazepam] on both frequency and amplitude of uterine contraction were still significantly higher than just before oxytocin and PDSGF2alfa [effect of diazepam alone]. The effect of diazepam was also examined in-vitro on isolated non-pregnant rat uterus. It was found that diazepam in concentrations ranging from 0.125-16 microg/ml produced significant concentration-dependent reduction in the height of contraction elicited by either acetylcholine [1 micro g/ml] or KCl [2.2 mg/ml]. The concentration of diazepam that produced 50% reduction of acetylcholine and KCl responses [IC50] were 1.8 microg/ml and 0.75 micro g/ml respectively. In the presence of flumazenil, diazepam produced nearly the same relaxant effect on acetylcholine-induced contraction with an IC50 value of 2 microg/ml which was not significantly different from that obtained in the absence of flumazenil [1.8 micro g/ml]. In KCl depolarized uterine horns, diazepam [2 micro g/ml] with rightward shift of the concentration response curve of CaCl2, indicating a Ca2+ antagonistic activity for diazepam. It could be concluded that pretreatment with diazepam during near term pregnancy may lead to serious complications during the process of labour-induction by oxytocin or PGF2alfa