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PubMed2000

The nature of the sheep chorionic oxytocic substance.

The effects of infusions of fresh sheep placenta in normal saline and the filtrate obtained therefrom after boiling for 15 min were investigated on guinea-pig and rat uteri, other mammalian non-vascular smooth muscles and the cardiovascular system, noting their responses to the infusion/filtrate in the presence or absence of various inhibitors or agonists. Solvent partition, acute toxicity and thin layer chromatography (TLC) studies were also performed. It was found that the infusion/filtrate had oxytocic activity independent of histamine and muscarinic receptors. It had H(1) receptor activity agonist action on the guinea-pig ileum, antagonized adrenaline-induced contractions in the vas but unlike bradykinin did not relax rat duodenum. It induced vasoconstriction in the rat hindquarters, depressed cat blood pressure but had positive inotropic effect on the guinea-pig Langendorff heart. Only the eluent from the least mobile of the five TLC bands on silica gel had oxytocic activity. It was concluded that the sheep chorionic oxytocic substance is not acetylcholine, histamine, 5-hydroxytryptamine, noradrenaline, adrenaline, prostaglandins F or E but is a peptide, which is not bradykinin, vasopressin or oxytocin.

Animals↗
PubMedDate not supplied

[A bioassay for the testing of the oxytocic effect of hormone analogs of the neurohypophysis and the pineal body].

An improved bioassay for the testing of oxytocic compounds by the use of myometrium layer preparations has been developed and proved with synthetic oxytocin. The oxytocic activity of synthetic analogues was testes with this bioassay and compared to oxytocin. The myometrial layer preparation was demonstrated to be reliable, the vitality of the tissue is found for more than 8 hours. The sensitivity of the bioassay is found in the region of 10(-11) Mol/l oxytocin, the maximum of the stimulation of muscle strips varied from 5 X 10(-5) IU/ml to 10(-4) IU/ml oxytocin in the organ-bath. The concentration of the myometrium strips showed two different phases. Only the initial phase can be used for this bioassay. The calculation of the results was afforded planimetrically and by measuring of the concentration-maximum during the testing period. The synthetic hormone analogues [1-desamino-4-alpha-aminobutyric acid] lysine-vasotocin (2) and [4 alpha-aminobutyric acid] lysine-vasotocin had oxytocic activity and the myometrium was activated to contractions at 10(-8) Mol/1. The analogue 2 was 5-10 more active than 3. The contraction maximum for both analogues was found between 5 X 10(-6) and 5 X 10(-5) Mol/l. The induction of the concentration for both analogues varied with the factor 10(5).

Animals↗
PubMedDate not supplied

Oxytocic activity of plasma and posterior pituitary lobe after ovariectomy and implantation of stilboestrol or progesterone tablets in female rats.

The purpose of this work was to compare the oxytocic activity of plasma and posterior pituitary lobe extract in rats after sham operation, ovariectomy and after subcutaneous implantation of stilboestrol or progesterone tablets in ovariectomized rats. On the 5th day after ovariectomy or implantation of hormones, sample of 2 ml of blood were obtained under urethane anaesthesia from the cephalic end of the right external jugular vein, and the animals were killed by decapitation. The posterior pituitary lobe was removed and homogenized in 0.9% NaCl solution acidified with glacial acetic acid. The oxytocic activity of plasma and extracts of the posterior pituitary lobe was determined by the method of Van Dongen and Hays on fragments of lactating rat mammary tissue. On the 5th day after ovariectomy or implantation of stilboestrol the oxytocic activity was found to be significantly increased in the plasma and posterior pituitary lobe, and after progesterone implantation it was decreased in the posterior pituitary lobe.

Animals↗
PubMedDate not supplied

Distribution of oxytocic and vasopressor activity in the rat diencephalon.

The oxytocic and vasopressor activity was studied in five 1 mm thick, horizontal sections of the rat diencephalon. The diencephalon was cut frozen in dry ice. The sections obtained from identical parts of the diencephalon of 10 rats were homogenized together in 0.9% NaCl solution acidified with glacial acetic acid. The homogenate was heated to 100 degrees C for 5 min and centrifuged. The oxytocic activity of extracts was determined in vitro by, the method of Holton using the rat myometrium. The vasopressor activity was determined in vivo recording blood pressure in the carotid artery of rat by the method of Dekańaski. Oxytocic activity was found in all five sections of diencephalon and vasopressor activity in only two sections. The first section included the median eminence and ventral hypothalamus together with the supraoptic nucleus, the second section included the the dorsal hypothalamus with paraventricular nucleus, the third section--the ventral thalamus, the fourth section--the middle part of thalamus, the fifth section--the dorsal thalamus.

Animals↗
PubMed1982

[The changes of human plasma ACTH and immunoreactive beta-endorphin during spontaneous or oxytocics induced/maintained labor and delivery (author's transl)].

To evaluate the effects of oxytocics on ACTH and Immunoreactive (IR)-beta-endorphin release, concentrations of these hormones in the plasma of 22 women during spontaneous labor, 22 women in labor who had received oxytocin and 19 women in labor who had received PG.F2 alpha at the time of vaginal delivery, were measured. Maternal ACTH and IR-beta-endorphin concentrations were elevated during spontaneous or oxytocics induced/maintained labor and peaked immediately after delivery and decreased two hours later. There were significant correlations between ACTH and IR-beta-endorphin concentrations during spontaneous labor and delivery (r = 0.921, p less than 0.0001), as well as in oxytocin or PG.F2 alpha induced/maintained labor and delivery (r = 0.833, r = 0.916, p less than 0.0001, respectively). The concentrations of ACTH and IR-beta-endorphin during PG-F2 alpha infusion were slightly higher than those seen in the other two types of labor. However, there was no significant difference in the levels of ACTH and IR-beta-endorphin among the three types of labor. Simultaneous maternal and umbilical cord plasma samples were obtained in 25 cases at delivery. However, there was no significant correlation between ACTH or IR-beta-endorphin concentrations in paired samples. These results suggest that 1) IR-beta-endorphin is secreted in parallel with ACTH, into the peripheral blood by the maternal pituitary gland in response to the stress of labor during all types of labor and delivery; 2) there is no significant difference in the response of ACTH and IR-beta-endorphin between spontaneous and oxytocics induced/maintained labor and delivery: 3) ACTH and IR-beta-endorphin in cord blood are not of maternal origin.

Adrenocorticotropic Hormone↗
PubMed1957

Oxytocic activity of basic (aminomethyl) derivatives of phenols and related compounds.

A series of piperidinomethyl and related derivatives of naphthols, substituted phenols and indoles has been tested for oxytocic activity, using in vitro and in vivo methods of assay. Some of the compounds possessed very high activity, exceeding that of ergometrine. Activity was not associated with any structural resemblance to the ergot alkaloids.Highest activity occurred with 2-piperidinomethyl derivatives of phenols, among which maximum potency was conferred by substitution, at both the 4- and 5- positions, by methyl or ethyl or by linkage of these positions to form an indane derivative. In all series, piperidinomethyl derivatives were more active than those formed with other bases and methylation in the position alpha- to the nitrogen atom augmented the activity of both piperidine and morpholine derivatives. Among 2'-methyl piperidinomethyl phenols, the (-) form was more active than the (+). Acylation or alkylation of the phenolic hydroxyl group did not affect activity.The oxytocic activity was specific, the compounds being less effective upon other forms of smooth muscle. Effects upon blood pressure and respiration of a central nature were observed.

Blood Pressure↗
PubMed1991

Oxytocics for the prevention of post-partum haemorrhages. A review.

Secale alkaloids, oxytocin and prostaglandins are used to prevent post-partum haemorrhage (post-partum haemorrhage defined as blood loss greater than or equal to 500 ml). Any oxytocic drug administered in the third stage of labour reduces the blood loss with approximately 40% and hence the incidence of post-partum haemorrhage from 10 to 6%. Therefore, routine active management of the third stage with an oxytocic drug is strongly advocated. Because of the fewest side-effects oxytocin is regarded as the best drug available at this moment.

Female↗
PubMed1988

Choice of oxytocic preparation for routine use in the management of the third stage of labour: an overview of the evidence from controlled trials.

Prophylactic use of oxytocics reduces the risk of postpartum haemorrhage by about 40%. The analysis presented in this paper assesses which oxytocic preparation is associated with the least risk of postpartum haemorrhage and examines the relative effects of different preparations on the length of the third stage, the risk of manual removal of the placenta, blood pressure and other side-effects. A mixture of oxytocin and ergometrine (Syntometrine) appears to be the safest and most effective prophylactic of the alternatives which have been compared, but the quality of the evidence is not satisfactory. There is scope for a randomized comparison of Syntometrine with oxytocin to obtain unbiased and more precise estimates of their relative effects on postpartum haemorrhage, blood pressure and unpleasant side-effects.

Clinical Trials as Topic↗
PubMed2001

Oxytocics reverse the tocolytic effect of glyceryl trinitrate on the human uterus.

OBJECTIVES: To investigate the effect of glyceryl trinitrate on isolated human pregnant uterine strips and whether the uterine relaxation induced by glyceryl trinitrate could be reversed by oxytocics used in current clinical practice. DESIGN: In vitro pharmacological study. SETTING: Department of Obstetrics & Gynaecology, National University of Singapore, National University Hospital. PARTICIPANTS: Eighteen women who delivered by caesarean section at term. METHODS: Myometrial strips were preloaded with an initial tension of 1.5g in organ baths containing Krebs-Henseleit solution which was aerated with oxygen in 5% carbon dioxide and maintained at 37 degrees C, pH 7.4. The effect of glyceryl trinitrate was studied in strips displaying regular spontaneous contractions. The ability of oxytocin, ergometrine or prostaglandin F2alpha to stimulate uterine contractions was assessed in strips where uterine activity was significantly inhibited by glyceryl trinitrate. RESULTS: Glyceryl trinitrate reduced the amplitude and frequency of spontaneous uterine contractions in a concentration-dependent manner, although the sensitivity of the myometrial strips varied considerably from one specimen to another. The concentration of glyceryl trinitrate producing complete inhibition of myometrial contractions ranged from 44-705 microM. In the presence of glyceryl trinitrate which markedly depressed spontaneous contractions, oxytocin (20 mU/mL), ergometrine (6.15 microM) and prostaglandin F2alpha (6.15 microM) were capable of reversing the uterine activity to either higher than or the untreated level of contractility. CONCLUSIONS: This study demonstrates that glyceryl trinitrate is a potent uterine relaxant in vitro and that the tocolytic effect could be reversed with ease by oxytocics.

Dinoprost↗
PubMed1983

Oral oxytocics for induction of labor. A randomized study of prostaglandin E2 tablets and demoxytocin resoriblets.

A randomized comparative study of 387 consecutive patients admitted for induction of labor was carried out using two orally administered oxytocics (prostaglandin E2 tablets (Prostin) or Demoxytocin resoriblets for buccal administration (Sandopart)), the results of which are reported here. One-hundred and twenty-three cases were suitable for primary amniotomy; of these 48 were given PGE2 tablets and 75 received demoxytocin resoriblets. In a further 264 cases, primary amniotomy was inadvisable and of these, 133 patients were allotted to the PGE2 treatment group and 131 to treatment with demoxytocin. A significantly higher success rate was observed (p less than 0.05) in the PGE2 group in cases where primary amniotomy had been carried out, as compared with the demoxytocin group. Parturition was successfully induced in 82.0% of the patients given PGE2 tablets, as against only 63.4% of those receiving demoxytocin following 2 days of stimulation without primary amniotomy. This difference is statistically significant at the 0.001 level, and presumably due to the highly significant difference (p less than 0.0001) between patients with a Bishop score of 5 or less, where induction was successful in 75.4% given PGE2 tablets, in contrast to a success rate of only 36.7% in patients receiving demoxytocin resoriblets. No difference was observed in the success rate between the two treatment groups when the Bishop score was 6 or more. No difference was recorded in the incidence of fetal distress, instrumental delivery or low Apgar score between the two treatment groups. However, a higher incidence of vomiting and diarrhea were observed in patients treated with PGE2 tablets (11%) as compared with those receiving demoxytocin (1.5%). There was no difference with regard to the induction-delivery time, nor to the different stages of labor between otherwise comparable treatment groups when the induction was successful. It is concluded in respect of induction of labor using orally administered oxytocics that PGE2 (tablets) are preferable to demoxytocin (resoriblets) as it is the more effective of the two.

Administration, Oral↗
PubMed1958

Third international standard for posterior pituitary; re-named third international standard for oxytocic, vasopressor and antidiuretic substances in 1956.

In October 1955, stocks of the Second International Standard for Posterior Pituitary were running low and the Department of Biological Standards of the National Institute for Medical Research, London, was asked to proceed with the arrangements for an international collaborative assay of material for the Third Standard. A single 142-g batch of posterior-pituitary-lobe powder was obtained and distributed in ampoules, in approximately 30-mg quantities. Samples were sent to 19 laboratories in 10 countries. In all, 185 assays were carried out, 122 for oxytocic activity, 53 for vasopressor activity and 10 for antidiuretic activity.On the basis of the results, which were analysed statistically at the National Institute for Medical Research, it was agreed that the potency of the Third Standard (re-named International Standard for Oxytocic, Vasopressor and Antidiuretic Substances in 1956, in view of the recent synthesis of oxytocin and vasopressin) should be expressed as 2.0 International Units per milligram. The International Unit therefore remains unchanged as 0.5 mg of the dry powder.

Biological Assay↗
PubMed1987

Fenprostalene in cattle: Evaluation of oxytocic effects in ovariectomized cows and abortion potential in a 100-day pregnant cow.

Four ovariectomized cows were used to compare the uterotonic (oxytocic) properties of the prostaglandins F2alpha analogue fenprostalene to cloprostenol and PGF2alpha-tromethamine salt (dinoprost). Uterine activity was measured by electromyography with the duration and magnitude of activity quantified by microcomputer. The administration of 1 mg of fenprostalene to estradiol primed animals significantly increased uterine motility for approximately 19 h. This was significantly longer than the duration observed for either cloprostenol (500 mug, i.m., 8.9 h) or dinoprost (25 mg, i.m., 7.7 h). However, the level of activity was similar for the 3 compounds tested, with postinjection levels of oxytocic effect averaging 369 % for treated animals compared to 100 % for controls. Therefore, the difference in effects for the three prostaglandins may be due more to pharmacokinetic properties rather than to different potencies of the three compounds. In addition, a pregnant cow (100 d gestation) was treated with fenprostalene (1 mg, s.c.). Fenprostalene treatment resulted in unchanged uterine activity for a 6-h period, followed by a four-fold increase in genital tract activity which lasted for 12 h. Thereafter, activity was inhibited for one day, followed by a sharp increase in uterine activity leading to abortion within 66 to 72 h after fenprostalene injection. The placenta was expelled 7 days after treatment.

Journal Article↗
PubMed2000

The effects of herbal oxytocics on the isolated "stripped" myometrium model.

Decoctions of Agapanthus africanus and Clivia miniata are used as oxytocic agents in South African traditional herbal medicine. Aqueous extracts of A. africanus and C. miniata leaves have been shown to possess similar uterotonic activities in the isolated whole uterus preparation. The uterus however, comprises a myometrial and an endometrial layer and the activity of both oxytocin and the prostaglandins differs in these layers. The aim of this study was to determine the uterotonic activity of the herbal remedies in an endometrium-free preparation (i.e. "stripped" myometrium) and, if active, whether this effect could be related to prostaglandin synthesis or to interaction with specific receptors. The effects of the herbal extracts were tested on the isolated "stripped" rat myometrium preparation. Both herbal extracts caused a direct contractile response by the isolated tissue. Pretreatment of the myometrium with either plant extract augmented the initial response to acetylcholine. Preincubation with atropine inhibited the response to cumulative dosage of Agapanthus extract but had no effect on the response to Clivia. Indomethacin administration did not affect the response of the myometrium to cumulative dosage of acetylcholine, oxytocin or Clivia extract but inhibited the response to Agapanthus extract. These results clearly indicate that the Agapanthus and Clivia herbal extracts exhibited uterotonic activity in this model. The study illustrates that the "stripped" myometrium model has successfully differentiated between the mechanisms of action of two herbal oxytocics compared to the whole uterus preparation where their uterotonic activity was thought to be similar.

Animals↗
PubMedDate not supplied

The hypothalamic and neurohypophysial vasopressor and oxytocic content as influenced by alpha-adrenergic blockade in stressed rats.

The hypothalamic and neurohypophysial vasopressor and oxytocic content as influenced by alpha-adrenergic blockade in stressed rats. Acta physiol. pol., 1985, 36 (3): 193-200. The effects of phenoxybenzamine (PBA; an alpha-adrenergic blocker) on hypothalamic and neurohypophysial vasopressin and oxytocin were investigated in stressed rats. Immobilization resulted in a decrease of both vasopressor and oxytocic activities in the hypothalamus and neurohypophysis, whereas in rats, exposed to cold the vasopressin and oxytocin content in the hypothalamo-neurohypophysial system was increased. Under treatment with PBA the vasopressin and oxytocin content in the neurohypophysis was diminished in stressed (both immobilized and cold-exposed) rats when compared to respective groups of untreated animals subjected to appropriate kind of stress. The response of the vasopressinergic and oxytocinergic neurones seems, therefore, to be dependent on the type of stress. The alpha-adrenergic transmission is probably in some way involved in the mechanisms of modified neurohypophysial function in stressed animals.

Animals↗
PubMedDate not supplied

The effect of the milking process on oxytocic activity in the blood plasma of cows during oestrous.

The purpose of this work was to compare the oxytocic activity of plasma in oestrous cows during milking and for the first and second days following oestrous. Oxytocic activity of blood plasma was measured by the in vitro rat mammary cube assay of van Dongen and Hays. During oestrous, signigicantly lower amounts of oxytocin are released into the bloodstream of cows following milking as compared with the control values.

Animals↗
PubMed1999

Pharmacological basis for the use of the antivenene water soluble extract of Diodia scandens as a laxative, oxytocic agent and a possible aphrodisiac in traditional medicine practice in eastern Nigeria.

The effects of the antivenene fraction of an ethanol extract of Diodia scandens on some mammalian smooth muscles were investigated. On the guinea-pig ileum, the extract was shown to be a partial agonist acting via muscarinic receptors. Acetylcholine (ACh) was 2.5 x 10(5) times more potent. On the pregnant guinea-pig uterus, the extract induced concentration-dependent increases in the force of contraction and tonus. Oxytocin and ergometrine were respectively 10(6) and 10(3) times more potent. The extract, at subliminal concentrations, potentiated ACh and adrenaline-induced contractions in the guinea-pig was deferens. It also induced dose-related vasodilatation in the rat hindquarters and depressed the blood pressure in the anaesthetized cat. It was concluded that these pharmacological actions offer some scientific explanation for the use of Diodia scandens in traditional medicine as a laxative and as an oxytocic agent. It is suggested that the extract could enhance erection and ejaculatory processes in the male, thus accounting for its regular use by some elderly males.

Acetylcholine↗
PubMed1994

A simple alternative to parenteral oxytocics for the third stage of labor.

OBJECTIVE: To determine the effect of nipple stimulation on uterine activity during the third stage of labor. METHODS: Randomized controlled study comparing; (i) 15 min of nipple stimulation (n = 6), (ii) routine syntometrine injection (n = 3), (iii) no action/control (N = 5). Uterine activity was continuously measured using the placenta as an in-situ hydrostatic bag connected to a pressure transducer. RESULTS: Compared to controls uterine pressure was higher during nipple stimulation (103 mmHg vs. 70.8 mmHg, P = 0.04). The duration of the third stage and blood loss tended to be reduced with nipple stimulation compared to controls (20.3 vs. 12.3 min) and (257 vs. 166 ml) respectively but was not significant. Similar differences were observed between syntometrine and control groups. CONCLUSIONS: For women in developing countries where parenteral oxytocics are not available, nipple stimulation might reduce the incidence of postpartum hemorrhage. A larger trial now seems warranted.

Adult↗
PubMed2001

History and use of oxytocics.

The most widely known oxytocic drug that can be used for the induction of labor or post-partum is oxytocin. In 1954, the american biochemist Vincent du Vigneaud was the first to describe an octapeptide amide with the hormonal activity of oxytocin. One year later, he was able to synthesize this octapeptide amide. In the same year he received the Nobel prize for his work in the field of biochemistry. A reprint of his brilliant publication is reproduced [with kind permission of the editors of the J Am Chem Soc]. With slight changes in structure, du Vigneaud was able to synthesize not only oxytocin, but also vasopressin. In our paper, however, we will focus on oxytocin only, as it is this synthetic hormone that has gained considerable importance in obstetrics. It is used for prevention of PPH as well as for induction of labour.

Female↗