Absorption, Distribution and Excretion
Absorption is rapid and complete after oral or intramuscular administration.
Thought to be eliminated by non-renal mechanisms (i.e. hepatic metabolism, excretion in feces)
Ergonovine maleate and methylergonovine maleate are rapidly absorbed after oral or im administration.
Uterine contractions are usually initiated within 5-15 minutes following oral administration, within 2-5 minutes after im injection, and immediately following iv injection of ergonovine or methylergonovine. Uterine contractions persist for 3 hours or longer after oral or im administration and for 45 minutes after iv injection of either drug.
Little is known about the elimination of ergonovine or methylergonovine. It has been suggested that the drugs are principally eliminated by nonrenal mechanisms (i.e., metabolism in the liver, excretion in feces).
The aim of this investigation was to assess the pharmacokinetics and bioavailability of ergometrine in six human male subjects after an oral dose of 0.200 mg and after an intravenous dose of 0.075 mg of ergometrine maleate. A large variation in bioavailability of between 34% and 117% in the six volunteers was observed. The lag time was also subject dependent and ranged between 0.0073 hr (0.4 min) and 0.47 hr (28 min). After intravenous administration, the pharmacokinetic profile can be described by a two-compartment model. The distribution half-life t1/2 alpha is 0.18 +/- 0.20 hr, the elimination half-life t1/2 beta is 2.06 +/- 0.90 hr, the total body clearance (CL) amounts to 35.9 +/- 13.4 L hr-1 and the steady-state volume (Vss) of distribution is 73.4 +/- 22.01. After oral administration, the pharmacokinetic profile can be described by a one-compartment model. The absorption half-life t1/2 abs is 0.19 +/- 0.22 hr, and the elimination half-life t1/2 beta 1.90 +/- 0.16 hr. This study with oral ergometrine shows such a large interindividual variability in bioavailability that the oral route of administration does not seem not to be the most reliable means of accurate dosing in preventing post-partum hemorrhage.

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Metabolism / Metabolites
Hepatic.
Hepatic.
Route of Elimination: Thought to be eliminated by non-renal mechanisms (i.e. hepatic metabolism, excretion in feces)
Half Life: t_{1/2 α}=10 minutes; t_{1/2 β}=2 hours

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Biological Half-Life
t_{1/2 α}=10 minutes; t_{1/2 β}=2 hours
The aim of this investigation was to assess the pharmacokinetics and bioavailability of ergometrine in six human male subjects after an oral dose of 0.200 mg and after an intravenous dose of 0.075 mg of ergometrine maleat. ... After intravenous administration, the pharmacokinetic profile can be described by a two-compartment model. The distribution half-life t1/2 alpha is 0.18 +/- 0.20 hr, the elimination half-life t1/2 beta is 2.06 +/- 0.90 hr ... After oral administration, the pharmacokinetic profile can be described by a one-compartment model. The absorption half-life t1/2 abs is 0.19 +/- 0.22 hr, and the elimination half-life t1/2 beta 1.90 +/- 0.16 hr. ...
Plasma concentrations of methylergonovine appear to decline in a biphasic manner. ... Following iv administration of ergonovine to adults, the half-life of the drug in the initial phase (t1/2 alpha) reportedly is about 10 minutes and the half-life in the terminal phase (t1/2 beta) is about 2 hours.

Toxicity Summary
Ergoline alkaloids tend to act as a group, producing complex and variable effects of partial agonism or antagonism at adrenergic, dopaminergic, and serotonergic receptors. Variables relating to these effects are influenced by the agent, dosage, species, tissue, physiological, and endocrinological state, and experimental conditions. In particular, ergoline alkaloids have been shown to have the significant affinity towards the 5-HT1 and 5-HT2 serotonin receptors, D1 and D2 dopamine receptors, and alpha-adrenergic receptors. This can result in a number of different effects, including vasoconstriction, convulsions, and hallucinations. Ergometrine is also known to have a non-receptor specific oxytocic activity. (A2914, A2915, A2916)

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Ergonovine is no longer marketed in the United States. Ergonovine given in the immediate postpartum period lowers serum basal prolactin and suckling-induced prolactin possibly increases. However, the prolactin level in a mother with established lactation may not affect her ability to breastfeed. Ergonovine appears to decrease the rate of breastfeeding. Ergonovine is probably best avoided in mothers who wish to nurse, relying instead on suckling-induced oxytocin release to hasten uterine involution.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
In one study, a single oral dose of ergonovine maleate 0.2 mg in 12 nonbreastfeeding women on day 3 postpartum caused a 10 to 20% drop in average serum prolactin levels between 0.5 and 2.5 hours after the dose. The authors expressed concern that repeated doses of ergonovine could suppress lactation.
Ten women who were given ergonovine 0.2 mg 3 times daily from day 1 to 7 postpartum were compared to 6 women who did not receive the drug. None of the women breastfed their infants. Serum prolactin levels were significantly lower in the treated women by day 2 postpartum and persisted through the 7 days of the study. Seven of the 10 treated women developed breast engorgement and had milk letdown and 3 had progressive inhibition of lactation. In 2 additional women who were nursing their infants, a single dose of 0.2 mg of ergonovine intravenously blunted the response of serum prolactin to suckling.
In a nonrandomized study, 11 women with normal deliveries were given an intramuscular injection of either oxytocin 5 units plus ergonovine 0.5 mg (n = 5) or 5 units of oxytocin alone (n = 6). Serum prolactin levels were lower in the women given ergonovine from 0.5 to 2.5 hours.
In a randomized, but nonblinded, controlled trial, women thought to be at low risk of postpartum hemorrhage were given either ergonovine 0.5 mg intravenously following birth of the infant (n = 197) or no drug (n = 135). Serum prolactin levels obtained in the period of 48 to 72 hours postpartum did not differ between the groups, but fewer of those who received ergonovine were still breastfeeding at 4 weeks postpartum than those who did not.
A retrospective review of obstetrical records of 18,165 records of mothers giving birth in Wales found that use of intravenous or intramuscular ergonovine during the third stage of labor as a uterotonic reduced the odds of the mother breastfeeding at 48 hours postpartum. The reduction was 36% in the overall sample and 49% for primiparous mothers.

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Interactions
Concomitant use of ergot alkaloids and human immunodeficiency virus (HIV) protease inhibitors, delavirdine, or nevirapine is contraindicated.
Caffeine enhances action of ergot alkaloids in treatment of migraine... /Ergot alkaloids/
Peripheral and coronary vasoconstriction may be antagonized by nitrites or papaverine. /Ergot alkaloids/
This study investigated modulation of the cytochrome P450 3A (CYP3A4)-mediated metabolism of ergotamine (ET) by ergonovine and dihydroergotamine. Liver microsomes were prepared from rats treated i.p. for 4 d with: low (10 mM) or high (100 mM) levels of dexamethasone (DM10 and DM100), dihydroergotamine, ergonovine, or control. Cytochrome P450 activity was evaluated using ET and its isomers as substrate. Ergotamine was converted to its metabolites at rates of 0.385 or 0.535 (SE = 0.040) nM/microg protein/min when incubated with liver microsomes from DM10 or DM100 treated rats, respectively. These rates were higher than for rats on other treatments. Induction of CYP34A activity was not greater for ergonovine or dihydroergotamine treatments than for controls. Both ergonovine and dihydroergotamine treatments inhibited in vitro CYP3A4 activity in a dose dependent manner producing quadratic inhibition curves.
Ergonovine maleate significantly attenuated dopamine-HCl induced hypotension in urethane anesthetized rabbits. Doses of 0.09 & 0.18 mg/kg intraarterially administered to dogs competitively inhibited dopamine-induced mesenteric vasodilation.

Therapeutic Uses
Oxytocics
Ergonovine maleate and methylergonovine maleate are used for the prevention and treatment of postpartum hemorrhage caused by uterine atony. The drugs appear to be equally effective for these purposes; however, many clinicians prefer methylergonovine to ergonovine because the former drug may produce hypertension less frequently than does the latter drug. /Not included in US product label/
Ergonovine maleate has been used as a provocative test for the diagnosis of variant angina. The drug has been used to precipitate coronary artery spasm in patients with suspected variant angina. /Not included in US product label/
Ergonovine and methylergonovine should not be used for the induction or augmentation of labor.
MEDICATION (VET): Oxytocic ... /used/ in control of postpartum uterine hemorrhage, removal of fluid from atonic uteri, to help prevent prolapsed uteri, and judiciously in terms of timing to aid in suturing uterus after cesarean section or in replacing everted uterus.

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Drug Warnings
When administered in correct doses to carefully selected patients who are closely monitored, there is little risk of serious adverse systemic effects in patients receiving ergonovine or methylergonovine.
Hypertension may occur following administration of ergonovine or methylergonovine, especially when administered iv undiluted or too rapidly or when used in conjunction with regional anesthesia or vasoconstrictors; hypertension may occur less frequently with methylergonovine than with ergonovine. Some patients, especially eclamptic or previously hypertensive patients, may be unusually sensitive to the hypertensive effects of the drugs; generalized headaches, severe arrhythmias, seizures, and cerebrovascular accidents have been associated with ergonovine- or methylergonovine-induced hypertension in these patients. Hypotension also has been reported.
Since ergonovine or methylergonovine may cause serious adverse cardiovascular effects, some clinicians recommend that the drugs not be used in patients with hypertension, heart disease, venoatrial shunts, mitral valve stenosis, or obliterative vascular disease.
Because prolonged use of ergonovine or methylergonovine may produce ergotism in sensitive individuals, prolonged use of the drugs should be avoided.
For more Drug Warnings (Complete) data for ERGONOVINE (14 total), please visit the HSDB record page.

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Pharmacodynamics
Ergonovine belongs to the group of medicines known as ergot alkaloids. These medicines are usually given to stop excessive bleeding that sometimes occurs after abortion or a baby is delivered. They work by causing the muscle of the uterus to contract.

C19H23N3O2

325.179

60-79-7

60-79-7;

443884

Plates or needles
Tetrahedra from ethyl acetate, fine needles from benzene; tends to form solvated crystals

1.8

3

3

3

24

535

3

C[C@@H](CO)NC(=O)[C@H]1CN([C@@H]2CC3=CNC4=CC=CC(=C34)C2=C1)C

WVVSZNPYNCNODU-XTQGRXLLSA-N

InChI=1S/C19H23N3O2/c1-11(10-23)21-19(24)13-6-15-14-4-3-5-16-18(14)12(8-20-16)7-17(15)22(2)9-13/h3-6,8,11,13,17,20,23H,7,9-10H2,1-2H3,(H,21,24)/t11-,13+,17+/m0/s1

(6aR,9R)-N-((S)-1-hydroxypropan-2-yl)-7-methyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide

SecacorninErgometrine Neofemergen Ergobasine

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)