Absorption, Distribution and Excretion
Absorption is rapid and complete after oral or intramuscular administration. Clearance is believed to be primarily via non-renal routes (e.g., hepatic metabolism, fecal excretion). Ergonovine maleate and mesergotine maleate are rapidly absorbed after oral or intramuscular administration. Uterine contractions typically begin within 5–15 minutes after oral administration, within 2–5 minutes after intramuscular administration, and immediately after intravenous administration of ergonovine or mesergotine. Uterine contractions can last for 3 hours or longer after oral or intramuscular administration, and up to 45 minutes after intravenous administration. Limited knowledge is available regarding the clearance pathways of ergonovine or mesergotine. Studies have shown that these drugs are primarily cleared via non-renal routes (i.e., hepatic metabolism, fecal excretion). This study aimed to evaluate the pharmacokinetics and bioavailability of 0.200 mg ergonovine orally and 0.075 mg ergonovine maleate intravenously in six male subjects. The results showed that bioavailability varied considerably among the six subjects, ranging from 34% to 117%. The lag time also varied among subjects, ranging from 0.0073 hours (0.4 minutes) to 0.47 hours (28 minutes). Following intravenous administration, the pharmacokinetic characteristics were described using a two-compartment model. The distribution half-life t_1/2α was 0.18 ± 0.20 hours, the elimination half-life t_1/2β was 2.06 ± 0.90 hours, the total clearance (CL) was 35.9 ± 13.4 L/h, and the steady-state volume of distribution (V_ss) was 73.4 ± 22.01 L. Following oral administration, the pharmacokinetic characteristics were described using a one-compartment model. The absorption half-life (t_1/2abs) was 0.19 ± 0.22 hours, and the elimination half-life (t_1/2β) was 1.90 ± 0.16 hours. This oral ergonovine study indicates significant individual variability in bioavailability, therefore oral administration does not appear to be the most reliable and precise route of administration for preventing postpartum hemorrhage. Metabolism/Metabolites: Hepatic metabolism. Elimination route: believed to be eliminated via non-renal mechanisms (i.e., hepatic metabolism, fecal excretion). Half-life: t_1/2α = 10 minutes; t_1/2β = 2 hours. Biological half-life: t_1/2α = 10 minutes; This study aimed to evaluate the pharmacokinetics and bioavailability of ergonovine maleate after oral administration of 0.200 mg and intravenous injection of 0.075 mg in six male subjects. ...After intravenous administration, its pharmacokinetic characteristics can be described using a two-compartment model. The distribution half-life t_1/2α is 0.18 ± 0.20 hours, and the elimination half-life t_1/2β is 2.06 ± 0.90 hours. ...After oral administration, its pharmacokinetic characteristics can be described using a one-compartment model. The absorption half-life t_1/2abs is 0.19 ± 0.22 hours, and the elimination half-life t_1/2β is 1.90 ± 0.16 hours. ...
The concentration of ergonovine in plasma appears to decrease in a biphasic manner. It has been reported that after intravenous injection of ergonovine in adults, the drug's half-life in the initial phase (t_{1/2 α}) is approximately 10 minutes, and its half-life in the terminal phase (t_{1/2 β}) is approximately 2 hours.

Toxicity Summary
Ergoline alkaloids typically act as a whole, producing complex and variable local agonist or antagonist effects on adrenergic, dopaminergic, and serotonergic receptors. These effects are influenced by drug type, dosage, species, tissue, physiological and endocrine state, and experimental conditions. In particular, ergoline alkaloids have been shown to have significant affinity for 5-HT1 and 5-HT2 serotonin receptors, D1 and D2 dopamine receptors, and α-adrenergic receptors. This can lead to a variety of different effects, including vasoconstriction, convulsions, and hallucinations. Ergoline is also known to have non-receptor-specific oxytocin activity. (A2914, A2915, A2916) Effects During Pregnancy and Lactation ◉ Overview of Use During Lactation Ergoline has been discontinued in the United States. Immediate postpartum administration of ergoline can lower basal serum prolactin levels and may increase lactation-induced prolactin levels. However, for mothers who have established lactation, prolactin levels may not affect their ability to breastfeed. Ergonovine appears to reduce breastfeeding rates. For mothers who wish to breastfeed, it is best to avoid ergonovine and instead rely on suckling-induced oxytocin release to accelerate uterine involution.
◉ Effects on breastfed infants
No relevant published information found as of the revision date.
◉ Effects on lactation and breast milk
In one study, 12 non-breastfeeding women who received a single oral dose of 0.2 mg ergonovine maleate on postpartum day 3 experienced a 10% to 20% decrease in mean serum prolactin levels within 0.5 to 2.5 hours after administration. The authors are concerned that repeated administration of ergonovine may suppress lactation.
Ten women who received 0.2 mg ergonovine three times daily from postpartum day 1 to day 7 were compared with six women who did not receive the drug. None of the women were breastfeeding. In the treatment group, serum prolactin levels were significantly lower on day 2 postpartum and remained so until the end of the study (7 days). Seven out of ten women in the treatment group experienced breast engorgement and the milk ejection reflex, while three experienced milk suppression. Two breastfeeding women showed a diminished prolactin response to suckling after a single intravenous injection of 0.2 mg ergonovine. In a non-randomized study, eleven women with normal deliveries received intramuscular injections; five received 5 units of oxytocin combined with 0.5 mg ergonovine, and six received 5 units of oxytocin alone. In a randomized but unblinded controlled trial, women at low risk of postpartum hemorrhage were randomized to two groups: one group received an intravenous injection of 0.5 mg ergonovine after birth (n=197), and the other group received no medication (n=135). There was no significant difference in serum prolactin levels between the two groups within 48 to 72 hours postpartum, but women treated with ergonovine were more likely to continue breastfeeding at four weeks postpartum than untreated women. A retrospective study of the obstetric records of 18,165 women in Wales found that the use of intravenous or intramuscular ergonovine as a uterotonic agent during the third stage of labor reduced the likelihood of breastfeeding within 48 hours postpartum. The reduction was 36% in the overall sample and 49% in primiparous women.
Interactions

Concomitant use of ergonovine with HIV protease inhibitors, deraviridine, or nevirapine is contraindicated.
Caffeine may enhance the migraine-treating effects of ergonovine…/Ergonovine/
Nitrites or papaverine may antagonize peripheral and coronary vasoconstriction. /Ergonovine/
This study investigated the regulatory effects of ergonovine and dihydroergotamine on cytochrome P450 3A (CYP3A4)-mediated ergotamine (ET) metabolism. Liver microsomes were prepared by intraperitoneal injection of low-concentration (10 mM) or high-concentration (100 mM) dexamethasone (DM10 and DM100), dihydroergotamine, ergonovine, or a control group for 4 consecutive days. Cytochrome P450 activity was assessed using ET and its isomers as substrates. When incubated with liver microsomes from rats treated with DM10 or DM100, the rates of ergotamine conversion to its metabolites were 0.385 and 0.535 (SE = 0.040) nM/μg protein/min, respectively. These rates were higher than those in other treatment groups. The CYP34A activity induction levels in the ergonovine or dihydroergotamine treatment groups were not significantly different from the control group. Both ergonovine and dihydroergotamine inhibited in vitro CYP3A4 activity in a dose-dependent manner, exhibiting a quadratic inhibition curve. Ergonovine maleate significantly alleviated dopamine hydrochloride-induced hypotension in rabbits anesthetized with ethyl carbamate. Intra-arterial injection of ergonovine at doses of 0.09 and 0.18 mg/kg in dogs competitively inhibits dopamine-induced mesenteric vasodilation.

Therapeutic Uses
Oxytocin
Ergonovine maleate and methylergonovine maleate are used to prevent and treat postpartum hemorrhage caused by uterine atony. Both drugs appear to be equally effective in these respects; however, many clinicians prefer methylergonovine maleate over ergonovine maleate because the former may cause hypertension less frequently than the latter. /Not included on US product label/
Ergonovine maleate has been used as a provocation test for diagnosing variant angina. This drug has been used to induce coronary artery spasm in patients suspected of having variant angina. /Not included on US product label/
Ergonovine and methylergonovine should not be used to induce or intensify labor.
Drug (Veterinary): Oxytocin…/used for/controlling postpartum uterine bleeding, clearing fluid accumulation in uterine atony, helping to prevent uterine prolapse, and, as appropriate, for suturing the uterus after cesarean section or repositioning a prolapsed uterus.

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Drug Warning
When administered at the correct dose to carefully selected and closely monitored patients, the risk of serious systemic adverse reactions in patients receiving ergonovine or methylergonovine is minimal.
Hypertension may occur after use of ergonovine or methylergonovine, especially when administered intravenously as undiluted or too rapidly, or in combination with regional anesthesia or vasoconstrictors; the incidence of hypertension caused by methylergonovine may be lower than that caused by ergonovine. Some patients, especially those with eclampsia or a history of hypertension, may be abnormally sensitive to the pressor effects of the drugs; in these patients, ergonovine or methylergonovine-induced hypertension has been associated with generalized headache, serious arrhythmias, seizures, and cerebrovascular accidents. Hypotension has also been reported.
Because ergonovine or methylergonovine can cause serious cardiovascular adverse reactions, some clinicians recommend that patients with hypertension, heart disease, venous-atrial shunts, mitral stenosis, or occlusive vascular disease should not use these drugs.
Because prolonged use of ergonovine or methylergonovine may lead to ergot poisoning in sensitive individuals, these medications should be avoided.
For more complete data on ergonovine (14 in total), please visit the HSDB records page.

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Pharmacodynamics
Ergonovine belongs to the ergot alkaloid class of drugs. These drugs are commonly used to stop excessive bleeding that sometimes occurs after miscarriage or childbirth. Their mechanism of action is to cause uterine muscle contractions.

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.)