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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although only about 8 per cent of pregnancies end prematurely, as much as 75 per cent of perinatal deaths are due to prematurity. Since it is difficult to identify the predisposing factors in individual cases and to prevent the premature onset of labor, it is necessary to try to arrest such labor when it occurs. A theoretical scheme for the mechanism of labor in the human subject is presented. This permits the identification of four possible points of attack: (1) replacement of progesterone to reduce the myometrial sensitivity to oxytocin, (2) administration of beta-mimetic agents to relax the uterus and make it unresponsive to stimuli, (3) administration of ethanol to block oxytocin secretion, and (4) administration of anti-inflammatory drugs to inhibit prostaglandin synthesis. Results obtained with ritodrine, a beta-mimetic agent, and with ethanol are presented as illustration. Ritodrine gave somewhat better results than ethanol, possibly because the treatment was continued after discharge of the patients.
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PMID:Prevention of prematurity. 1 89

Ritodrine hydrochloride was administered parenterally to pregnant ewes during spontaneous or oxytocin-induced uterine activity. The effects of ritodrine on the uterus and cardiovasculature were assessed both with and without simultaneous administration of either alpha or beta blockade. Ritodrine was found to be an effective inhibitor of both spontaneous and induced uterine activity. Ritodrine did cause maternal tachycardia but no significant hypotension. Alpha-adrenergic blockade did not influence the effects of ritodrine. Beta blockade with propranolol reversed the uterine and cardiovascular effects of ritodrine, whereas beta blockade with practolol reversed the cardiovascular effects without interfering with the inhibition of uterine activity produced by ritodrine.
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PMID:Effect of ritodrine on uterine activity, heart rate, and blood pressure in the pregnant sheep: combined use of alpha or beta blockade. 1 90

In this study we compare the uterine contractility and beta-adrenergic receptor effects of identical doses of ritodrine administered intermittently or continuously for 24 hours in pregnant sheep. Ritodrine was administered intravenously to five animals as a pulse, 16 micrograms/kg every 1.5 hours, whereas five other animals received ritodrine as a continuous infusion of 0.18 microgram/kg/min. Ritodrine plasma concentrations at steady state were comparable in both groups and averaged 18 ng/ml. Animals receiving ritodrine pulses demonstrated no alteration of myometrial beta-adrenergic receptors or adenylyl cyclase activity, and ritodrine inhibited oxytocin-induced contractility comparably at 4 and 24 hours. Animals receiving ritodrine continuously had a significant decrease in myometrial beta-adrenergic receptors and adenylyl cyclase activity, yet ritodrine inhibition of oxytocin-induced uterine contractility was sustained for 24 hours. Oxytocin receptors were not affected by ritodrine administration and were similar in both groups. At the dose studied, oxytocin-induced contractions are comparably inhibited by ritodrine for 24 hours whether the drug is given continuously or in a pulsatile fashion.
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PMID:Comparison of pulsatile and continuous ritodrine administration: effects on uterine contractility and beta-adrenergic receptor cascade. 184 3

The effect of a recently developed oxytocin antagonist dTVT, i.e. deamino-[2-D-tyrosine(OEt)-4-threonine-8-ornithine] oxytocin on uterine contraction of pregnant rats was studied in vitro. The following results were obtained. 1. dTVT treatment did not affect spontaneous PGE2- or PGF2 alpha-stimulated contraction, while it slightly suppressed PGE1 analogue (Gemeprost)-stimulated contraction of the uterus. 2. Following treatment with dTVT (5-50 micrograms/ml), oxytocin-stimulated uterine contraction was gradually and slowly suppressed, resulting in an attenuation curve. Ritodrine treatment, on the other hand, rapidly suppressed spontaneous uterine contraction as well as contraction stimulated by various oxytocics. Suppression of oxytocin-stimulated uterine contraction by dTVT took much longer (14.8 +/- 1.1 min) to take effect than that by ritodrine (less than 1 min).
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PMID:Effects of oxytocin antagonist (dTVT) and ritodrine on spontaneous and oxytocics-induced uterine contractions in pregnant rats. 195 39

The existing data on prostaglandins indicate that they are involved in human parturition and regulation of fetoplacental blood flow. The interference of endogenous and exogenous oxytocin and prostaglandins and, on the other hand, betamimetics, which are commonly used during pregnancy, in the regulation of these phenomena is poorly understood. The production of prostaglandins by fetal placental cotyledons was studied using an in vitro perfusion technique. Isolated cotyledons were perfused without (control) or with oxytocin (200 pg/ml, 2000 pg/ml) or the betasympathomimetic drug ritodrine (10 micrograms/ml, 50 micrograms/ml). The release of prostaglandin F2 alpha (PGF2 alpha), prostaglandin E2 (PGE2), 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane B2 (TxB2) was measured by radioimmunoassay. The release of prostaglandins was also studied during a recovery period after the drug infusion. Oxytocin at a concentration of 200 pg/ml significantly decreased the release of PGF2 alpha. A higher concentration of oxytocin did not cause any changes in prostaglandin production. During ritodrine infusion the perfusion pressure was decreased, but the addition of ritodrine to the perfusion medium had no effect on prostaglandin release. During the recovery period, after ritodrine infusion, the release of PGF2 alpha was significantly decreased. It is suggested that oxytocin at the physiological concentration may protect the fetus from adverse effects of PGF2 alpha before labor in decreasing the release of PGF2 alpha, yet this small decrease in formation of PGF2 alpha is obviously of minor clinical importance because the perfusion pressure remained constant. Ritodrine had no effect on prostaglandin release and so the decrease in the perfusion pressure is probably the result of beta 2-receptor stimulation.
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PMID:The effect of oxytocin and betamimetic stimulation on prostaglandin release in perfused human fetal placenta. 346 20

Puerperal uteri were stimulated by oxytocin, the uterine motility was recorded by transcervical catheter techniques, maternal pulse and blood-pressure were recorded continuously or intermittently. Oral tocolytics as Gynipral (Hexoprenaline), Partusisten (Fenoterol), Spiropent (Clenbuterol) and Prepar (Ritodrine) were administered orally in single or double dose. The inhibitory effect of these drugs were recorded, evaluated from the records and calculated statistically concerning their significant differences. It could be demonstrated that only Hexoprenaline in a three time higher dose than used usually and Partusisten in a dose of 10 and 20 mg were able to reduce uterine motility for more than 50%. All other substances definitely had an inhibitory effect on the puerperal uterus, but inhibition was not stronger than 30%. Cardiovascular side-effects were discussed. The question, if oral given betamimetics are effective in the treatment of threatening premature labour could not be answered definitively, but there are doubts according this study concerning the dose and the repetition of it for this purpose.
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PMID:[The efficacy of oral betamimetics using an oxytocin-stimulated puerperal model (author's transl)]. 704 Jan 60

We have measured the concentrations of circulating oxytocin and the 13, 14-dihydro, 15-keto-metabolite of prostaglandin F2 alpha (PGFM) in women during preterm labor. Twelve women were given intravenous ethanol and 11 women received intravenous ritodrine for the prevention of preterm birth. Blood samples were obtained before and 1/2, 1, 2, 4, 12, and/or 24 hours after treatment began. On admission, the plasma concentrations of both oxytocin and PGFM were raised over levels observed in women with normal pregnancies of similar gestational age, 25 to 36 weeks. The initial oxytocin level was 58.5 +/- 8.2 pg/ml (mean +/- SE, n = 23) and the mean initial PGFM level was 264 +/ 33.1 pg/ml (n = 15); both values were significantly higher than in 10 control subjects (17.4 +/- 4.8 and 156 +/- 21.8 pg/ml, respectively). During infusion of ethanol, the plasma oxytocin level fell rapidly, the levels at 1/2 and 1 hour after infusion being significantly lower than before the infusion (29.0 +/- 5.5 and 27.8 +/- 3.5 pg/ml, respectively). The plasma oxytocin level remained low in women in whom the treatment arrested labor and prevented preterm birth (n = 8) but rose 2 to 4 hours after the infusion began in women in whom the treatment failed to arrest labor (n = 4). Ritodrine, on the other hand, had no significant effect on circulating oxytocin levels. The plasma PGFM level decreased significantly during ritodrine treatment only in the successfully treated patients. Ethanol had no consistent effect on plasma PGFM levels in the four patients in whom PGFM levels were measured. In the ritodrine-treated patients, the plasma PGFM level was positively correlated with the frequency of uterine contractions whereas in the ethanol-treated patients a correlation of plasma oxytocin to the frequency of contractions was observed. Thus, oxytocin secretion is increased during preterm labor, and the release of prostaglandin F is also increased. While it is not possible to determine whether any or both of these oxytocic agents actually trigger preterm labor, both seem to play a role in its mechanism.
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PMID:Plasma levels of oxytocin and 13, 14-dihydro-15-keto prostaglandin F2 alpha in preterm labor and the effect of ethanol and ritodrine. 714 97

The action of the uterine relaxant ritodrine on placental, myometrial and cardiac blood pools has been examined during spontaneous and oxytocin-induced uterine activity. 113mIndium was injected intravenously and the blood pools were measured by recording gamma-activity externally. After i.v. injection of Ritodrine, the typical blood pool changes in labor were inhibited. Thereafter, placental and myometrial blood pools increased more than due to inhibition of labor alone. Simultaneously, there was a corresponding decrease in cardiac blood pool indicating an increase in cardiac output. The rapid inflow of blood in the uteroplacental region after Ritodrine indicates an improved hemodynamic situation. This action could be of benefit in emergency situations in a hyperactive ischaemic uterus during labor.
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PMID:Hemodynamic changes in placenta, myometrium and heart after administration of the uterine relaxant ritodrine. 736 29

The purpose of this study was to determine in vivo the dose response relationship between beta-adrenergic receptor (BAR) agonist concentration and various elements of the BAR cascade: receptor density, hormone-stimulable adenylyl cyclase activity, and contraction inhibition. A previously described, chronically-catheterized ovine model was used. Ritodrine was infused continuously over 24 h in 22 mixed-breed sheep. Each animal received a single, constant infusion rate. Myometrial biopsies were obtained before and after the drug infusions. BAR density was determined using tritiated dihydroalprenolol. Adenylyl cyclase activity was determined using the Gilman competitive protein-binding assay. Intermittent oxytocin boluses were given into the maternal aorta and contractile response was determined. Infusion rates of 0.06-4.0 micrograms/kg/min yielded steady-state ritodrine serum concentrations of 5-168 ng/ml. No significant correlation was found between the ritodrine concentration and the magnitude of decrease in BAR density. Significant correlations existed, however, between the ritodrine concentration and both the magnitude of decrease in adenylyl cyclase activity and the loss of contraction inhibition. There was no correlation noted between the BAR cascade alterations and the loss of contraction inhibition. Despite significant reductions in receptor density (down regulation) and dose-related reductions in hormone-stimulable adenylyl cyclase activity (uncoupling), ritodrine at low concentrations was still able to inhibit oxytocin-induced contractions, i.e., tachyphylaxis did not occur. Tachyphylaxis appeared to correlate only with the serum ritodrine concentration. Hence, alterations in the BAR cascade do not necessarily equate with a loss of end-organ response (tachyphylaxis). Previous concepts based on in vitro studies about the interaction of the BAR agonist with its receptor, the subsequent generation of intracellular messengers, and the resultant end-organ response may not apply in the intact animal.
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PMID:Alterations in ovine myometrial beta-adrenergic cascade do not mediate tachyphylaxis to ritodrine. 879 87

Preterm labour is a major cause of perinatal mortality and morbidity. However, during the past 40 years of clinical studies and despite the use of multiple therapeutic agents, the rate of preterm birth has not drastically declined. In 1991, it was estimated that in the US approximately 116,000 women admitted with acute episodes of preterm labour were treated each year with ritodrine, which is the first drug approved by the US FDA and still remains the standard therapy for treating preterm labour. Ritodrine (Yutopar( trade mark )) stimulates the beta(2)-adrenergic receptor throughout the body, causing an inhibitory action in different tissues that, among other side effects, also leads to an attenuation of uterine contractility. More recently, a new therapeutic agent, atosiban (Tractocile( trade mark )), a peptidic oxytocin receptor antagonist, has been introduced to the market. However, the use of the various pharmacological agents to treat preterm labour remains restricted, due to lack of uterine selectivity, low efficacy and potentially serious side effects for the mother or the foetus. Therefore, there is an urgent need to develop drugs with myometrial selectivity that would allow long-lasting inhibition of labour and prolong pregnancy up to a stage when good foetal maturation raises the chances of survival. One of the major obstacles hampering the development of new therapeutic agents is the marked inter-species difference in terms of preterm labour physiology, which complicates the preclinical evaluation of new candidate molecules in animal models of disease. In this review, the authors will provide a comprehensive update of past, current and new approaches for the management of preterm labour, including beta(2)-adrenergic agonists, calcium channel blockers, oxytocin antagonists, prostaglandin antagonists and other potential therapeutics. For each of the therapies used today, the review will cover the mechanism of action, benefit and adverse effects, and discuss the promise and potential benefits of new emerging therapeutic agents.
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PMID:Preterm labour: an overview of current and emerging therapeutics. 1287 Nov 40


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