Influence of a combination of ritodrine and nifedipine on the isolated rat uterus.
Studies were undertaken to evaluate the efficacy of the beta 2-adrenergic agonist ritodrine and the calcium channel blocker nifedipine, alone and in combination, for inhibition of contraction in isolated rat uterine strips. Both compounds produced a dose-dependent reduction of area under the curve. When contractions were produced by oxytocin, a 26% reduction was observed with 0.144mcg of ritodrine and a significant 68.1% decrease was produced with 1.44mcg of ritodrine. Contraction frequency (contractions per ten minutes) was not significantly affected. Prostaglandin F2 alpha-induced contractions were significantly inhibited 27.1% and 62.2% by 1.44mcg and 14.4mcg of ritodrine, respectively. Also, contraction frequency was significantly affected by both concentrations. Inhibition of area under the curve of oxytocin-induced contractions produced by nifedipine was 39.3% for 0.05mcg and 78.4% (P less than 0.05) for 0.50mcg. Contraction frequency was unaffected. Prostaglandin F2 alpha-induced contractions were significantly attenuated by 60% and 86% with nifedipine (0.50mcg and 5.02mcg, respectively); contraction frequency was significantly reduced from 15 to 2 contractions per ten minutes by 5.02mcg. Oxytocin-induced contraction was attenuated 39.8% by a combination of ritodrine 0.144mcg and nifedipine 0.05mcg; contraction frequency was unaffected. Area under the curve and contraction frequency of oxytocin-induced contractions were significantly decreased by a combination of ritodrine 0.144mcg and nifedipine 0.50mcg (89.8% reduction; decrease in frequency from 12 contractions in control to 4 contractions post-inhibitory agent). Significant attenuation of prostaglandin F2 alpha-induced contractions was produced by ritodrine 1.44mcg and nifedipine 0.50mcg. Area under the curve decreased by 73.2% and frequency was reduced from 13 to 8 contractions. A combination of ritodrine 1.44mcg and nifedipine 5.02mcg also produced significant decreases in area under the curve (85.3%) and frequency (13 contractions in control to 1 contraction after compounds were added). Because the mechanisms of action of these two agents are different, it is reasonable to suggest that they be used in combination to control premature labor. The results of this study suggest they may provide inhibition of contraction superior to either agent alone, and could therefore provide more effective inhibition and possibly reduce untoward side effects common to ritodrine therapy.
Gallagher
L A
LA
Department of Pharmacology, Temple University School of Pharmacy, Philadelphia, Pennsylvania 19140.
Gautieri
R F
RF
D000818:Animals; D015237:Dinoprost / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D009543:Nifedipine / Q000494:pharmacology*; D010121:Oxytocin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012312:Ritodrine / Q000494:pharmacology*; D014590:Uterine Contraction / Q000187:drug effects*
D000431:Ethanol; D010121:Oxytocin; D015237:Dinoprost; D012312:Ritodrine; D009543:Nifedipine