Misoprostol

Prostaglandin EP2 Receptors

This compound binds to and stimulates prostaglandin EP2 receptors. wikipedia.org EP2 receptors are typically coupled to the stimulatory G protein (Gs), and their activation leads to the activation of adenylyl cyclase and a subsequent increase in intracellular cyclic adenosine monophosphate (cAMP) levels. oncotarget.comyorku.ca Activation of EP2 receptors can have various effects depending on the tissue, including smooth muscle relaxation and modulation of immune responses. drugbank.comwikipedia.org

Prostaglandin EP3 Receptors

This compound binds to and stimulates prostaglandin EP3 receptors. wikipedia.org The EP3 receptor is a key target for this compound's actions, particularly in inducing uterine contractions and inhibiting gastric acid secretion. mdedge.comnih.govderangedphysiology.com EP3 receptors are unique among EP receptors as they can couple to multiple G proteins, including Gi, Gs, and Gq, leading to diverse downstream signaling effects depending on the splice variant and cellular context. oncotarget.comyorku.ca Activation of Gi-coupled EP3 receptors inhibits adenylyl cyclase, leading to a decrease in intracellular cAMP. oncotarget.comderangedphysiology.com EP3 receptors also play a role in calcium mobilization through pathways involving phosphoinositol turnover. mdedge.com

Prostaglandin EP4 Receptors

This compound also binds to and stimulates prostaglandin EP4 receptors. wikipedia.org Similar to EP2 receptors, EP4 receptors are primarily coupled to the stimulatory G protein (Gs), and their activation leads to increased intracellular cAMP levels via adenylyl cyclase activation. oncotarget.comyorku.ca EP4 receptor activation has been implicated in various physiological processes, including smooth muscle relaxation, immune modulation, and potential roles in cell proliferation and differentiation. drugbank.comresearchgate.net

Differentiation from Prostaglandin E2 Receptor Activation

While this compound activates EP2, EP3, and EP4 receptors, it is a synthetic analog of PGE1 and its receptor binding profile can differ from that of the naturally occurring prostaglandin E2 (PGE2). wikipedia.orgyorku.ca PGE2 acts on all four EP receptors (EP1, EP2, EP3, and EP4) with varying affinities, generally showing higher affinity for EP3 and EP4 compared to EP1 and EP2. oncotarget.com this compound, on the other hand, does not activate the EP1 receptor. wikipedia.org Although this compound can activate the same receptors as PGE2, its affinities for these receptors are generally lower than those of PGE2. oncotarget.comyorku.ca This differential receptor activation profile contributes to this compound's specific pharmacological effects and may result in a more restricted range of actions compared to PGE2 or other analogs that activate all four EP receptors. wikipedia.org

Adenylate Cyclase Inhibition and Cyclic AMP Levels in Parietal Cells

In gastric parietal cells, this compound primarily exerts its inhibitory effect on acid secretion by interfering with the adenylate cyclase signaling pathway. nih.govnih.gov Histamine stimulates acid secretion by activating histamine H2 receptors, which are coupled to stimulatory G proteins (Gs) that activate adenylate cyclase, leading to an increase in intracellular cyclic AMP (cAMP) levels. researchgate.net this compound, acting as a prostaglandin analog, binds to prostaglandin receptors (likely EP-3 receptors) on parietal cells. These receptors are coupled to inhibitory G proteins (Gi), which, upon activation by this compound, inhibit adenylate cyclase activity. nih.govresearchgate.net This inhibition leads to a reduction in the formation of cAMP. nih.govnih.gov Studies have shown that this compound noncompetitively inhibits cAMP formation in response to histamine in isolated parietal cells, with an IC50 value similar to that for the inhibition of histamine-stimulated acid secretion. nih.gov This suggests a close relationship between the antisecretory action of this compound and its ability to reduce histamine-stimulated cAMP formation, likely by interfering with the coupling between histamine H2 receptors and adenylate cyclase. nih.gov

Phosphoinositol Turnover and Calcium Mobilization in Myometrial Cells

In myometrial cells, this compound binding to EP-3 receptors induces an increase in intracellular phosphoinositol turnover and calcium mobilization. mdedge.commdedge.comthe-hospitalist.org This process leads to an increase in intracellular free calcium, which is a critical step in triggering actin-myosin contractility in smooth muscle cells. mdedge.commdedge.comthe-hospitalist.org The increase in intracellular calcium is propagated between myometrial cells through gap junctions, facilitating coordinated contractions. mdedge.commdedge.comthe-hospitalist.org While EP1 receptor activation is also associated with increased phosphoinositol turnover and calcium mobilization leading to smooth muscle contraction, EP3 receptors are known to inhibit adenylate cyclase and cAMP production via Gi proteins. researchgate.net

VEGF Signaling Pathway Modulation

Network pharmacology studies suggest that this compound can modulate the VEGF signaling pathway. nih.govajrh.info The VEGF signaling pathway is crucial for angiogenesis, regulating endothelial cell proliferation, migration, and survival. mdpi.complos.org While some research indicates that the action of mifepristone plus this compound on blood vessels in human decidua may be mediated by factors other than VEGF, network analysis points to a potential interaction. nih.govajrh.infonih.gov The VEGF pathway involves the binding of VEGF to its receptors (VEGFRs), leading to the activation of downstream signaling cascades such as Raf-MEK-MAPK, PI3K/AKT, and ERK1/2/FAK, which influence endothelial cell function. mdpi.commdpi.com HSP90AA1, identified as a core target of this compound, has been shown to play a role in VEGF-mediated signaling by interacting with eNOS and promoting PI3K/AKT pathway activation, which is essential for endothelial cell survival. mdpi.com

Calcium Signaling Pathway Modulation

This compound has been shown to modulate calcium signaling pathways in various cell types. In myometrial cells, it increases intracellular calcium leading to contraction. mdedge.commdedge.comthe-hospitalist.org In neuronal-type cells, this compound can elevate intracellular calcium levels via a protein kinase A (PKA)-mediated pathway, with the EP4 receptor potentially playing an inhibitory role. yorku.canih.gov Furthermore, research in neonatal cardiomyocytes suggests that this compound can attenuate hypoxia-induced proliferation by influencing perinuclear calcium signaling and promoting nuclear calcium accumulation. researchgate.netahajournals.orgresearchgate.net This involves the modulation of Bnip3, a Bcl-2 family member, and its splice variants, which affect calcium transfer between the sarcoplasmic/endoplasmic reticulum and mitochondria. researchgate.netbiorxiv.org

NF-κB Signaling Pathway Modulation

Studies indicate that this compound can modulate the NF-κB signaling pathway. nih.govajrh.inforesearchgate.netnih.gov NF-κB is a key transcription factor involved in inflammatory responses and the regulation of various genes, including cytokines like TNF-α and IL-10. nih.govnih.gov this compound's anti-inflammatory actions have been linked to E2 prostanoid receptor-mediated increases in cAMP, activation of protein kinase A (PKA), and subsequent attenuation of NF-κB transcriptional activity. researchgate.net While this compound may not affect NF-κB nuclear translocation, it can significantly decrease transcriptional stimulation by NF-κB. nih.gov Chromatin immunoprecipitation studies have demonstrated that this compound treatment can alter transcription factor and RNA Polymerase II promoter binding, leading to changes in TNF-α and IL-10 mRNA levels. researchgate.netnih.govnih.gov

Identification of Core Therapeutic Targets (e.g., HSP90AA1, EGFR, MAPK1)

Network pharmacology studies have identified core therapeutic targets of this compound. nih.govajrh.inforesearchgate.net Among these core targets are Heat Shock Protein 90 Alpha A1 (HSP90AA1), Epidermal Growth Factor Receptor (EGFR), and Mitogen-Activated Protein Kinase 1 (MAPK1). nih.govajrh.inforesearchgate.net These targets are involved in various cellular processes, including protein phosphorylation, cell localization, and protein hydrolysis regulation processes. nih.govajrh.info Their modulation by this compound is suggested to contribute to its pharmacological effects, including its influence on pathways such as VEGF signaling, calcium signaling, and NF-κB signaling. nih.govajrh.info

Data Table: Core Therapeutic Targets of this compound

Note: This table summarizes information from network pharmacology studies identifying core targets and their potential involvement in pathways modulated by this compound. nih.govajrh.inforesearchgate.netmdpi.com

Functional and Pathway Enrichment Analyses (GO and KEGG)

Network pharmacology and molecular docking studies have been employed to investigate the multi-target mechanisms of this compound, particularly in the context of pregnancy termination. ajrh.infonih.gov These analyses aim to identify the key genes and pathways involved in this compound's effects.

Gene Ontology (GO) functional and KEGG pathway enrichment analyses have shown that this compound can modulate several signaling pathways. ajrh.infonih.gov These include the VEGF signaling pathway, calcium signaling pathway, and NF-κB signaling pathway. ajrh.infonih.gov The analyses suggest that this compound primarily interferes with processes such as protein phosphorylation, cell localization, and protein hydrolysis regulation. ajrh.infonih.gov

Research utilizing transcriptomics and proteomics in animal models has also applied GO and pathway enrichment analyses to understand the effects of medical abortion regimens including this compound. nih.gov These studies can reveal changes in gene and protein expression in uterine tissues and highlight affected pathways, such as cholesterol metabolism, arginine biosynthesis, cell apoptosis, and the FoxO signaling pathway. researchgate.net

Direct Stimulation of Uterine Smooth Muscle Contraction

This compound directly stimulates the contraction of smooth muscle cells in the uterine lining. drugbank.compatsnap.comuct.ac.za This is primarily achieved through the activation of prostaglandin EP receptors on myometrial cells. wikipedia.orgdrugbank.compatsnap.commdedge.comthieme-connect.de Activation of EP1 and EP3 receptors generally leads to smooth muscle contraction, while EP2 and EP4 receptors are typically associated with relaxation. conicet.gov.arthieme-connect.denih.govutoronto.ca this compound's binding to EP2, EP3, and EP4 receptors contributes to increased uterine contractility. wikipedia.orgthieme-connect.deutoronto.ca

The binding of this compound to myometrial EP-3 receptors, for example, induces an increase in intracellular phosphoinositol turnover and calcium mobilization. mdedge.com This rise in intracellular free calcium triggers the interaction of actin and myosin filaments, leading to muscle contraction. patsnap.comogmagazine.org.aumdedge.com

Collagen Degradation in Cervical Tissue

This compound contributes to cervical ripening, a process involving the softening and dilation of the cervix. wikipedia.orgdrugbank.com A key aspect of cervical ripening is the degradation of collagen in the connective tissue stroma of the cervix. drugbank.comresearchgate.netmdpi.com

Studies suggest that this compound softens the cervix, partly through an inflammatory response that leads to collagen degradation. researchgate.netmdpi.com This involves the release of matrix metalloproteinases (MMPs), such as MMP-8 and MMP-9, which break down collagen fibers. mdedge.comresearchgate.netmdpi.com Electron microscopy studies have shown that this compound treatment can result in pronounced splitting and disorganization of collagen fibers in cervical tissue. mdedge.com This process is similar to the changes observed during natural cervical ripening at term pregnancy and may involve the influx and activation of inflammatory cells. researchgate.netmdpi.com

Gap Junction Modulation in Myometrial Cells

The coordinated and efficient contraction of the myometrium during labor requires electrical synchrony between myometrial cells. ogmagazine.org.auuct.ac.zaiiarjournals.orgijabbr.com This synchrony is facilitated by gap junctions, which are low-resistance pathways allowing the flow of ions and small molecules between adjacent cells. ogmagazine.org.auuct.ac.zaiiarjournals.org

Toxicity Assessments (Acute and Chronic)

Acute toxicity studies in rodents and non-rodents have shown that the predominant sign of toxicity following single oral administration is diarrhea. hres.catga.gov.au Threshold doses for diarrhea varied among species, with values of 1.6 mg/kg in mice, 0.3 mg/kg in rats and rabbits, and 0.03 mg/kg in dogs. tga.gov.au Other acute toxic effects observed in animals are similar to those reported for other prostaglandins, including relaxation of smooth muscle, respiratory difficulties, and depression of the central nervous system. who.inthres.ca Microscopic changes in the stomach, such as hypertrophy of mucous cells and deepening of gastric pits, were also observed in single and repeat dose studies. tga.gov.au

Chronic toxicity studies, with durations up to 52 weeks in dogs and 2 years in rats, have also been conducted. tga.gov.aunih.gov Daily oral doses of up to 300 µg/kg in dogs and 9000 µg/kg in rats were evaluated. nih.gov Increased rectal temperatures were noted in dogs at doses of 100 and 300 µg/kg, while increased serum iron was observed in rats at 9000 µg/kg. nih.gov Increased stomach weights were seen in both dogs and rats in a dose-correlated manner, partly attributed to an increase in the number of normal epithelial cells (gastric hyperplasia). who.intnih.gov These gastric effects were reversible upon cessation of drug treatment. nih.gov Hyperostosis, primarily in the medulla of sternebrae, was observed in female mice following prolonged high-dose treatment, but this finding was not noted in long-term studies in dogs or rats and has not been seen in humans. who.intfda.govnih.govpfizermedicalinformation.com

Table 1: Summary of Acute Toxicity Findings in Animal Models

Note: This table is intended to be interactive in a suitable rendering environment.

Table 2: Summary of Chronic Toxicity Findings in Animal Models

Note: This table is intended to be interactive in a suitable rendering environment.

Mutagenicity and Carcinogenicity Studies

Evaluations of the mutagenic potential of this compound have been conducted using a battery of in vitro and in vivo assays. These studies, including tests for gene mutations and chromosomal damage, have consistently yielded negative results, indicating no evidence of genotoxicity. who.inttga.gov.aunih.govtga.gov.auhres.ca

Long-term carcinogenicity studies have been performed in rats and mice to assess the potential of this compound to induce tumors. In a 2-year study in rats, oral doses up to 2.4 mg/kg/day showed no evidence of an effect on tumor occurrence or incidence. tga.gov.aupfizermedicalinformation.comtga.gov.aunih.gov Similarly, a 21-month study in mice with oral doses up to 16 mg/kg/day did not reveal any tumorigenic effects. tga.gov.aupfizermedicalinformation.comtga.gov.au These doses represent significant multiples of typical human exposures. tga.gov.aupfizermedicalinformation.comtga.gov.au The most significant non-neoplastic finding in the rat carcinogenicity study was epithelial hyperplasia and hyperkeratosis of the gastric mucosa, which is considered characteristic of some prostaglandins. nih.gov

Reproductive Toxicity and Teratogenicity Mechanisms

Reproductive toxicity studies in animal models have demonstrated embryotoxicity and teratogenic potential for this compound, particularly at higher doses administered during organogenesis. tga.gov.autga.gov.aunih.gov Increased resorptions (embryotoxicity) were observed in rabbits at 1 mg/kg/day, in rats at 10 mg/kg/day, and in mice at 30 mg/kg/day when administered orally during the period of organogenesis. tga.gov.autga.gov.au

Teratogenic effects, such as an increased incidence of skeletal abnormalities, were noted in rabbits at 1 mg/kg/day, possibly due to maternal toxicity. tga.gov.autga.gov.au In mice, an increased incidence of skeletal abnormalities and cleft palate was observed at 30 mg/kg/day. tga.gov.au This dose in mice was found to be embryotoxic and teratogenic. tga.gov.au While some studies in rats and rabbits at certain dose levels did not find fetotoxic or teratogenic effects, other studies with prostaglandins have shown a dose-related increase in fetal malformations in rats. nih.govfda.gov

The mechanism underlying the observed reproductive and teratogenic effects in animals is thought to involve the pharmacological activity of this compound on uterine smooth muscle and the subsequent impact on fetal blood flow and development. nih.govnih.govwindows.netmedcraveonline.com

This compound is known to induce contractions of the smooth muscle fibers of the myometrium. who.intmims.com In pregnant animals, these intense uterine contractions can lead to compression of uterine and embryonic vessels. nih.govnih.govwindows.netresearchgate.netclinicalpub.comnih.gov This compression can disrupt blood flow to the placenta and the developing fetus, resulting in vascular disruption. researchgate.netpopcouncil.org

Animal studies indicate that temporary constriction of the uterine arteries, potentially caused by exposure to agents like this compound, can lead to hypoxic episodes in the embryo. clinicalpub.comresearchgate.net This vascular disruption and reduced blood flow are considered a plausible mechanism for the observed developmental abnormalities. medcraveonline.comresearchgate.netpopcouncil.org Experimental studies involving uterine manipulations in pregnant mice have demonstrated that such interventions during early gestation can result in hemorrhagic disruption of fetal structures, mediated by fetal hypoxia. clinicalpub.com

The disruption of fetal vascular supply due to this compound-induced uterine contractions can lead to embryonic hypoperfusion, characterized by decreased blood flow to fetal tissues. nih.govresearchgate.netresearchgate.net This reduced blood flow can result in tissue hypoxia, a state of oxygen deprivation. nih.govnih.govwindows.netresearchgate.netclinicalpub.comnih.gov

Hypoxia in the developing embryo can cause endothelial cell damage, hemorrhage, tissue loss, and subsequent abnormal development or structural abnormalities. researchgate.net The specific malformations observed can depend on the developmental stage at which the hypoxic event occurs. nih.govresearchgate.net Animal studies have shown that a single period of embryonic hypoxia can induce malformations similar to those associated with this compound exposure. nih.govwindows.netclinicalpub.com

In vitro studies using rat post-implantation embryo culture have shown that this compound can directly induce embryotoxic effects in a dose-dependent manner, leading to decreased embryo viability and function, including poor vascular development. researchgate.net Morphometric alterations were also observed in structures such as branchial arches, heart, and cephalic portions of the neural tube. researchgate.net These findings support the hypothesis that this compound can directly impact embryonic development, potentially through mechanisms related to vascular function and oxygenation.

Table 3: Summary of Reproductive Toxicity Findings in Animal Models

Note: This table is intended to be interactive in a suitable rendering environment.

Brainstem Ischemia and Limb Development Anomalies

Preclinical observations and studies in humans have suggested a link between in utero exposure to this compound and certain developmental anomalies, including those related to brainstem ischemia and limb development. The mechanism proposed involves uterine contractions induced by this compound, which can reduce blood flow to the uterine arteries, potentially leading to ischemic and hypoxic damage to the brainstem and contributing to limb development anomalies nih.gov.

Limb development anomalies associated with this compound exposure are often classified as "transverse," characterized by the absence of the distal part of a limb below the point where the aplasia begins nih.gov. These can include conditions such as arthrogryposis, clubfoot, distal reduction anomalies, constriction rings, syndactyly, or camptodactyly nih.gov. Studies have indicated that in utero exposure to this compound may increase the risk of developing transverse limb reduction anomalies nih.govnih.gov. Some research suggests this risk could be significantly higher compared to the general population nih.gov.

In a study involving infants exposed to this compound during the first trimester, deformities attributed to vascular disruption were observed researchgate.netcapes.gov.br. The uterine contractions induced by this compound are suggested to cause vascular disruption in the fetus, potentially leading to brainstem ischemia researchgate.netcapes.gov.br. The critical period for the pathogenesis of certain anomalies, such as Moebius sequence, is the first trimester, likely between gestational weeks four and eight scielo.br.

Moebius Sequence and Terminal Transverse Limb Defects

Moebius sequence is a rare congenital neurological disorder characterized by weakness or paralysis of multiple cranial nerves, most commonly the 6th (abducens) and 7th (facial) cranial nerves scielo.brpaojournal.com. This results in characteristic facial weakness and limited eye movement paojournal.com. Terminal transverse limb defects involve the absence of the end portion of a limb nih.gov.

Prenatal exposure to this compound has been associated with an increased risk of both Moebius sequence and terminal transverse limb defects nih.govresearchgate.net. Research, including systematic reviews and meta-analyses, has estimated a significantly increased odds ratio for these conditions following prenatal this compound exposure nih.govresearchgate.net.

The proposed mechanism linking this compound to Moebius sequence and terminal transverse limb defects involves vascular disruption during critical periods of embryonic development researchgate.netcapes.gov.brscielo.brpaojournal.com. Uterine contractions induced by this compound are thought to compromise blood flow, leading to ischemic damage in developing tissues, particularly the cranial nerve nuclei and limb buds nih.govresearchgate.netcapes.gov.brpaojournal.com. This vascular disruption sequence is considered a potential explanation for the observed pattern of anomalies scielo.brpaojournal.com.

Data from studies investigating congenital abnormalities in children exposed to this compound in utero have reported cases presenting with terminal transverse limb defects with or without Moebius sequence researchgate.netcapes.gov.br.

Modulation of Microsomal PGE2 Synthase (mPGES-1)

Microsomal prostaglandin E2 synthase-1 (mPGES-1) is a key enzyme involved in the synthesis of prostaglandin E2 (PGE2), a lipid mediator implicated in inflammation and various physiological processes nih.govresearchgate.net. PGE2 and its receptors (EP receptors) play a role in the central nervous system nih.govnih.govoncotarget.comresearchgate.netingentaconnect.com.

Research in APP/PS1 mice has shown that this compound administration can influence the expression of mPGES-1 and PGE2 receptors nih.govoncotarget.com. In these models, this compound was observed to reverse changes in the expression of mPGES-1, PGE2, and specific EP receptors (EP2, EP3, and EP4) nih.govoncotarget.com. Specifically, this compound administration decreased the expression of mPGES-1, PGE2, EP2, and EP4, while increasing EP3 expression in APP/PS1 mice nih.govoncotarget.com. These findings suggest that this compound's neuroprotective effects in this model may involve the modulation of the mPGES-1-PGE2-EP signaling pathway, particularly the activation of PGE2-EP3 signaling nih.govoncotarget.com.

Studies in aluminum-overload rats also indicated that this compound treatment could affect the PGES-PGE2-EP signal pathway, leading to a decrease in PGE2 levels and down-regulation of mPGES-1, EP2, and EP4 expression, alongside an up-regulation of EP3 expression nih.govresearchgate.netingentaconnect.com. This suggests a potential mechanism involving the rebuilding of the mPGES-1-PGE2-EP1-4 signal pathway balance nih.govingentaconnect.com.

Effects on Oxidative Stress Markers (e.g., SOD, MDA)

Oxidative stress is a significant factor in the pathogenesis of neurodegenerative diseases like Alzheimer's disease nih.govnih.gov. Markers such as superoxide dismutase (SOD) activity and malondialdehyde (MDA) content are commonly used to assess oxidative stress levels nih.govnih.govresearchgate.netmdpi.com. SOD is an important antioxidant enzyme, while MDA is an end-product of lipid peroxidation, indicating neuronal degeneration nih.govnih.gov.

Preclinical studies have investigated the effects of this compound on oxidative stress markers in animal models of neurodegeneration and other conditions. In APP/PS1 mice, this compound administration significantly reversed the decrease in SOD activity and the increase in MDA content observed in the hippocampus and cortex nih.govoncotarget.com. This suggests that this compound can reduce oxidative stress in the brain in this Alzheimer's disease model nih.govoncotarget.com.

Similarly, studies in rats with chronic aluminum overload showed that this compound treatment decreased MDA levels and increased SOD activity in hippocampal brain tissue, indicating a deceleration of oxidative stress nih.govresearchgate.netingentaconnect.com. This compound has also been shown to alleviate oxidative stress in the brain in models of systemic inflammation by decreasing cerebral MDA content and increasing antioxidant activity nih.govoncotarget.com.

Beyond neurodegeneration models, this compound has demonstrated effects on oxidative stress markers in other preclinical settings. For instance, studies on kidney injury in rats have shown that this compound treatment can lead to lower levels of MDA and higher activity of SOD and other antioxidant enzymes researchgate.netresearchgate.net. This suggests a broader antioxidative efficacy of this compound researchgate.net.

Labor Induction Studies

Misoprostol has been widely studied as an agent for inducing labor, with research focusing on its comparison to established methods, its impact on the duration of labor, and its effectiveness in preparing the cervix for delivery.

Clinical trials have consistently compared the efficacy of this compound with that of oxytocin and dinoprostone, the standard agents for labor induction.

Research indicates that oral this compound is more effective than a placebo and shows equivalency to intravenous oxytocin, vaginal this compound, and vaginal dinoprostone for labor induction. utoronto.ca When compared directly with oxytocin, particularly in cases of prelabor rupture of membranes (PROM), oral this compound has been shown to significantly shorten the induction-to-delivery time. barpetaogs.co.in Multiple studies have reported a shorter duration of labor with this compound compared to oxytocin. barpetaogs.co.in However, one meta-analysis noted that while vaginal this compound was more effective than oxytocin in achieving vaginal delivery within 24 hours, it was also associated with a higher risk of uterine hyperstimulation. nih.gov

In comparisons with dinoprostone, a prostaglandin E2 analogue, this compound has demonstrated several advantages. A randomized study found that vaginal this compound resulted in a significantly shorter median induction-to-delivery interval compared to dinoprostone gel (14.6 hours vs. 19.0 hours). fetalmedicine.org This study also noted a higher rate of vaginal delivery within 24 hours and a reduced need for oxytocin augmentation in the this compound group. fetalmedicine.org Another meta-analysis of seven randomized trials concluded that this compound use led to an approximately 50% reduction in the need for oxytocin augmentation compared to dinoprostone. ufrgs.br While cesarean section rates were generally comparable between the two groups in several studies, some research suggests a lower requirement for oxytocin with this compound. fetalmedicine.orgufrgs.brfrontiersin.org

Table 1: Comparison of this compound with Oxytocin and Dinoprostone for Labor Induction

A significant focus of research on this compound for labor induction has been its effect on the time from the start of induction to delivery.

Numerous studies have demonstrated that this compound can significantly shorten the induction-to-delivery interval. barpetaogs.co.infetalmedicine.org In a study involving women with PROM, the induction-to-delivery time was significantly less in the this compound group (309.15 ± 57.74 minutes) compared to the oxytocin group (367.45 ± 78.88 minutes). barpetaogs.co.in Similarly, another trial reported a mean induction-to-delivery interval of 13.8 hours with vaginal this compound. jogcr.com When compared with dinoprostone, this compound was associated with a shorter median induction-to-delivery interval (14.6 hours versus 19.0 hours). fetalmedicine.org A study comparing different doses of intravaginal this compound with intracervical dinoprostone found the induction-to-vaginal-delivery interval to be significantly lower with a 50 µg dose of this compound (13.8±6.62 hours) compared to a 25 µg dose (16.4±7.34 hours) or dinoprostone (16.3±7.49 hours). europeanreview.org

Table 2: Research Findings on this compound's Effect on Induction-to-Delivery Interval

This compound's utility in labor induction is closely linked to its ability to promote cervical ripening—the softening, dilating, and effacing of the cervix. clinicaltrials.govaafp.org

This compound acts on the intracellular matrix of the cervix, causing a breakdown of collagen fibrils, which leads to cervical softening. clinicaltrials.gov Research has shown a clear effect of this compound on cervical ripening, with one review noting a significant reduction in unchanged cervix at 12 to 24 hours compared to placebo. nih.gov Studies have demonstrated that both vaginal and oral this compound are effective for cervical ripening. utoronto.caclinicaltrials.gov A study comparing this compound with a combination of this compound and isosorbide mononitrate found that both were effective in achieving cervical ripening in terms of effacement, dilatation, and softening, though the combination was more effective. In a trial comparing different doses of this compound with dinoprostone, the 50 µg this compound group showed the maximum improvement in the Bishop's score, a measure of cervical favorability. europeanreview.org

Effects on Induction-to-Delivery Interval

Medical Abortion Research

This compound is a critical component in medical abortion regimens, both in combination with other drugs and as a standalone agent. Research has focused on establishing its efficacy and safety across different stages of pregnancy.

In settings where mifepristone is unavailable, research has explored the efficacy of this compound-only regimens for medical abortion. nih.gov

First Trimester: In the first trimester, this compound alone is considered a reasonable option for abortion. nih.gov A systematic review found that for gestations up to 63 days, the efficacy of this compound-only regimens ranged from 84% to 96%. nih.gov Another review of 38 studies reported that 78% of women who used a this compound-only regimen had a complete abortion without the need for surgical intervention. societyfp.org Research suggests that success rates are higher with repeated doses of this compound. bohrium.com Studies on self-managed abortions using this compound-only regimens have reported high effectiveness, with 93-99% of participants having complete abortions without surgical intervention. ibisreproductivehealth.org However, it is noted that a combined regimen of mifepristone and this compound is significantly more effective than this compound alone. bohrium.com

Second Trimester: For second-trimester terminations, this compound-only regimens have also been shown to be effective, although the chances of complications increase as pregnancy advances. nih.govgynuity.org One study on second-trimester termination found that vaginal this compound was 100% successful in inducing abortion, with the induction-to-expulsion interval varying with gestational age. gynaecologyjournal.com For pregnancies between 12 and 16 weeks, the majority of terminations occurred within 11 to 15 hours, while for those between 17 and 21 weeks, the peak expulsion time was between 16 to 20 hours. gynaecologyjournal.com Another study comparing a mifepristone-misoprostol combination with a this compound-only regimen in the second trimester found that while the combination was more effective, this compound alone could also be used effectively, albeit requiring a higher total dose. nih.gov A study in Hong Kong found that the mifepristone-misoprostol group had a shorter time to fetal expulsion (7.3 hours vs. 11.3 hours) and a higher proportion of successful abortions within 24 hours (95.7% vs 79.2%) compared to the this compound-alone group. hkjgom.org

Table 3: Efficacy of this compound-Alone Regimens for Medical Abortion

Combination Regimens with Mifepristone or Methotrexate: Synergistic Effects

The combination of this compound with other compounds, such as mifepristone or methotrexate, has been shown to produce synergistic effects, enhancing the efficacy of medical abortion.

Mifepristone, a progesterone receptor antagonist, when used in conjunction with this compound, has demonstrated high success rates in terminating early pregnancies. researchgate.netglobalauthorid.com Clinical trials have shown that this combination is more effective than this compound alone. nihr.ac.uk One study reported that a mifepristone-pretreatment group had a complete expulsion rate of 83.8% after one dose of this compound, compared to 67.1% in the group that received this compound alone. medscape.com Another trial found that the combination of mifepristone and this compound resulted in an 83% resolution rate for missed miscarriages, compared to 76% for those who received a placebo with this compound. nihr.ac.uk This combined regimen has also been associated with a reduced need for subsequent surgical intervention. nihr.ac.uk

Cervical Priming for Surgical Abortion

This compound is frequently utilized for cervical priming, or ripening, prior to surgical abortion to facilitate cervical dilation and reduce the risk of complications. bioline.org.brnih.gov

Clinical studies have demonstrated the efficacy of this compound for this purpose. Research has shown that both sublingual and vaginal administration of this compound are effective for cervical ripening in first-trimester surgical abortions. impactfactor.org A randomized controlled trial involving 600 women found that cervical priming with this compound before manual vacuum aspiration (MVA) significantly reduced the need for further cervical dilation and decreased the operative time. nih.gov Another study showed that the success of cervical dilatation with this compound increases with the dosage. bioline.org.br

Comparative studies have also been conducted. One trial compared this compound to laminaria, an osmotic dilator, and found that vaginal this compound resulted in greater mean cervical dilatation than laminaria, although the difference was not statistically significant. societyfp.org The use of this compound for cervical priming has been associated with high patient satisfaction rates. societyfp.org

Miscarriage Management Research (Incomplete and Missed Abortion)

This compound has been investigated as a medical alternative to surgical evacuation for the management of incomplete and missed miscarriages.

Efficacy of Uterine Evacuation

Research has established this compound as an effective method for uterine evacuation in cases of incomplete and missed abortion. nih.gov Studies have reported high success rates, with some indicating that this compound is as effective as surgical management. ijrcog.orgspringermedizin.de A review of literature found sufficient evidence to support this compound as a safe and effective means of non-surgical uterine evacuation for incomplete abortion in the first trimester. nih.gov

Success rates for complete uterine evacuation with this compound in cases of incomplete abortion have been reported to be between 80% and 99%. ipas.org For missed abortions, success rates with this compound are also high, particularly when preceded by mifepristone. ipas.orgmiscarriageassociation.org.uk One study found that pretreatment with mifepristone before this compound administration significantly increased the success rate of medical management for missed miscarriage. nihr.ac.ukmiscarriageassociation.org.uk

Reduction in Need for Surgical Intervention

A significant advantage of using this compound for miscarriage management is the potential to reduce the need for surgical intervention, such as dilation and curettage (D&C). medscape.com

In a randomized controlled trial comparing medical therapy with this compound to D&C for incomplete or inevitable abortion, the success rate for the this compound group was 96.3%, compared to 91.5% for the surgical group. medscape.com Another study on missed miscarriage found that combining mifepristone with this compound reduced the need for surgery to 17%, compared to 25% in the group that received a placebo with this compound. nihr.ac.uk Similarly, a study comparing this compound with surgical management for incomplete and missed miscarriage reported a 97% success rate in the medical treatment group, with only 3% requiring subsequent surgical evacuation. ijrcog.org

Postpartum Hemorrhage (PPH) Prevention and Treatment Research

This compound has been studied for its role in both the prevention and treatment of postpartum hemorrhage (PPH), a leading cause of maternal mortality worldwide. nih.gov

Comparative Efficacy with Oxytocin

Oxytocin is the standard uterotonic agent used for the prevention of PPH. However, research has explored this compound as an alternative, particularly in settings where oxytocin may not be readily available. nih.govclinicaltrials.gov

Several studies have compared the efficacy of this compound with oxytocin for PPH prevention. A double-blind randomized controlled trial found that the quantity of blood loss was lower in the group receiving this compound compared to the oxytocin group. nih.gov Another study concluded that oral this compound is as effective as intramuscular oxytocin in preventing PPH. scivisionpub.com However, some research has indicated no significant difference between the two in terms of the decrease in hemoglobin and hematocrit levels. nih.gov

The combination of this compound and oxytocin has also been investigated. A randomized clinical trial showed that the combined use of this compound and oxytocin significantly reduced postpartum blood loss and the incidence of PPH compared to oxytocin alone. medznat.ru

Community-Level Distribution and Impact on Maternal Mortality

This compound's stability at room temperature and ease of administration in tablet form make it a suitable intervention for preventing postpartum hemorrhage (PPH) in low-resource settings where a high proportion of births occur at home without skilled attendants. gynuity.org Community-level distribution programs have been implemented to increase access to this life-saving medication. gynuity.orgscispace.com

Research indicates that community-based distribution of this compound is a feasible, safe, and acceptable strategy. scispace.comdovepress.com Studies in several countries, including Nigeria, Uganda, and in rural areas of other nations like Ethiopia and Pakistan, have demonstrated that trained community health workers (CHWs) or traditional birth attendants (TBAs) can successfully distribute and administer this compound. gynuity.orgscispace.com In some programs, this compound is provided to pregnant women during their third trimester for self-administration after home births. gynuity.org

A significant concern regarding community distribution has been the potential for misuse or a reduction in facility-based deliveries. nih.gov However, evidence does not support these concerns. nih.govnih.gov A scoping review of 14 studies found no significant difference in the rates of facility delivery between groups that received community-based this compound and control groups. nih.govnih.gov Furthermore, the review, which included data from over 11,000 mothers, reported that self-administration of this compound before delivery was very low, occurring in less than 2% of cases, with no adverse outcomes from such misuse noted. nih.govnih.gov

The primary impact of these programs is the increased access to a uterotonic for PPH prevention for women who would otherwise not have it. scispace.com For instance, a study in northern Nigeria showed that the availability of this compound protected 83% of women who delivered at home against PPH. scispace.com Pooled analysis of randomized controlled trials has shown that this compound use in home or primary care settings can reduce the incidence of PPH by 24% and severe PPH by 41% compared to a placebo. nih.gov An integrative review of 18 programs reported that out of more than 86,000 women who took this compound, there were 51 maternal deaths, none of which were directly attributed to the use of the drug. healthynewbornnetwork.org

Table 1: Impact of Community-Based this compound Distribution Programs

Cervical Ripening Prior to Gynecological Procedures (e.g., Hysteroscopy, Dilation and Curettage)

This compound is widely researched for its efficacy in cervical ripening, or softening and dilating the cervix, before gynecological procedures such as hysteroscopy and dilation and curettage (D&C). nih.govnih.gov This pre-operative ripening can make the procedure easier to perform and may reduce the risk of complications like cervical injury and uterine perforation. nih.govnih.gov

For hysteroscopy , a systematic review and meta-analysis of 25 randomized controlled trials involving over 2,200 women found that using this compound beforehand significantly reduced the need for mechanical cervical dilatation. nih.gov The analysis also showed a greater initial cervical width and fewer complications, such as cervical lacerations and the creation of false passages, compared to placebo or no treatment. nih.gov The effectiveness of this compound can be influenced by factors like menopausal status, with some research suggesting it is more beneficial in premenopausal women. mdpi.com One study found that in postmenopausal women, pretreatment with estradiol enhanced the cervical dilating effect of this compound. mdpi.com

In the context of dilation and curettage (D&C) , research also supports the use of this compound for cervical priming. nih.gov A clinical trial in Iran demonstrated that this compound was effective for cervical ripening in premenopausal women undergoing diagnostic D&C for abnormal uterine bleeding. nih.gov The study highlighted that a ripened cervix simplifies the procedure and lowers the risk of trauma associated with mechanical dilation. nih.gov However, the efficacy may decrease with age, potentially due to lower estrogen levels. nih.gov

Table 2: Efficacy of this compound for Cervical Ripening in Gynecological Procedures

Prevention of NSAID-Induced Gastric Ulcers

This compound, a synthetic prostaglandin E1 analog, is approved for the prevention of gastric ulcers induced by nonsteroidal anti-inflammatory drugs (NSAIDs). nih.gov NSAIDs can deplete endogenous prostaglandins in the gastric mucosa, which play a protective role, making the stomach more susceptible to injury. nih.govacpjournals.org this compound works by replacing these protective prostaglandins. hres.ca

Numerous clinical trials have demonstrated its efficacy. A double-blind, placebo-controlled study found that this compound significantly reduced the incidence of NSAID-induced gastric ulcers. nih.gov In that study, ulcers developed in 21.7% of patients in the placebo group, compared to only 1.4% in the group receiving 200 micrograms of this compound. nih.gov Another 12-month, placebo-controlled trial confirmed that this compound decreases the cumulative development of these ulcers over the long term. tandfonline.com

Comparison with Proton Pump Inhibitors (PPIs)

Proton pump inhibitors (PPIs) are another class of drugs used to prevent NSAID-induced ulcers. has-sante.fr Comparative studies have been conducted to evaluate the relative efficacy of this compound and PPIs.

Generally, PPIs are often considered first-line treatment due to a better tolerability profile, as this compound is associated with gastrointestinal side effects like diarrhea and abdominal pain. has-sante.frnih.gov this compound is often recommended as a second-line treatment for patients who have contraindications or intolerance to PPIs. has-sante.fr

Table 3: Comparison of this compound and PPIs for NSAID-Induced Ulcer Prevention

Gastric Mucosal Cytoprotection Mechanisms

Beyond its role in inhibiting acid secretion, this compound exhibits a direct protective effect on the gastric mucosa, a mechanism known as cytoprotection. nih.govijpp.com This means it helps protect the stomach lining from damage by various irritants, including NSAIDs and alcohol, through mechanisms independent of acid reduction. nih.govhres.ca This cytoprotective action is thought to involve several key processes that enhance the mucosal defense system. hres.cancats.io These mechanisms include increasing mucosal blood flow, stabilizing vascular endothelium, and improving the capacity for mucosal regeneration. hres.cancats.io

Increased Mucus and Bicarbonate Secretion

A primary component of this compound's cytoprotective effect is its ability to stimulate the secretion of mucus and bicarbonate from the gastric and duodenal mucosa. nih.govnih.gov

Mucus Secretion: The mucus layer acts as a physical barrier, preventing damaging agents from reaching the epithelial cells. this compound has been shown to increase both the secretion and the thickness of this protective mucus layer. ncats.ionih.gov One study in healthy volunteers demonstrated that this compound significantly increased gastric mucus secretion in a dose-dependent manner. nih.gov Following administration, mucus secretion increased by 37%, 82%, and 95% during the basal period. nih.gov

Bicarbonate Secretion: Bicarbonate is secreted into the mucus layer, where it neutralizes acid that diffuses back from the stomach lumen, thus maintaining a near-neutral pH at the cell surface. this compound enhances the secretion of bicarbonate, further strengthening this chemical barrier. hres.cancats.io

These actions collectively fortify the gastroduodenal mucosal barrier, making it more resilient to injury from substances like NSAIDs. hres.ca

Thickening of Mucosal Bilayer

This compound, a synthetic prostaglandin E1 analog, demonstrates significant mucosal protective effects, a mechanism that is understood to involve the thickening of the mucosal bilayer. medicaldialogues.indrugbank.comnih.gov This cytoprotective action is attributed to several integrated processes. nih.gov Research indicates that this compound enhances the secretion of both mucus and bicarbonate. jove.com This leads to a thickening of the adherent mucus gel layer that protects the gastric and duodenal mucosa from aggressors like acid and pepsin. nih.gov

Studies in healthy human volunteers have quantified this effect. The administration of this compound resulted in a dose-dependent increase in gastric mucus secretion. hres.cahres.ca Similarly, this compound has been shown to stimulate duodenal bicarbonate secretion in a dose-dependent manner. hres.cahres.ca This enhanced secretion of mucus and bicarbonate contributes directly to the thickening and integrity of the mucosal barrier. medicaldialogues.indrugbank.comnih.gov The mechanism is thought to involve the replacement of depleted prostaglandins and an increase in mucosal blood flow, which aids in the preservation and regeneration of mucosal cells. hres.cahres.ca

Table 1: Effect of this compound on Gastric Mucus Secretion in Healthy Volunteers

Data sourced from a comparative study in eight healthy volunteers. hres.cahres.ca

Oral Administration

Following oral administration, this compound is absorbed rapidly and almost entirely from the gastrointestinal tract. This compound.org It undergoes extensive and swift first-pass metabolism, where it is de-esterified into its active metabolite, this compound acid. This compound.orgnih.gov Studies have shown that after an oral dose, the plasma concentration of this compound acid rises quickly, reaching its peak in approximately 12 to 30 minutes. This compound.orgnih.govjogi.co.in However, this peak is followed by a rapid decline, with levels decreasing significantly within 120 minutes and remaining low thereafter. This compound.orgjogi.co.in The quick onset of action is a key characteristic of this route. oup.com

Sublingual Administration

Sublingual administration involves placing the tablet under the tongue, where it dissolves and is absorbed through the sublingual mucosa. This compound.org This route allows for rapid absorption, bypassing the first-pass metabolism in the liver. This compound.orgoup.com Consequently, sublingual administration typically results in a higher peak plasma concentration (Cmax) compared to oral and vaginal routes. This compound.org The time to peak concentration (Tmax) for the sublingual route is comparable to the oral route, occurring at around 30 minutes. This compound.org Studies have indicated that the systemic bioavailability, as measured by the AUC, is greatest with sublingual administration, suggesting it is a highly potent route. oup.comoup.com

Buccal Administration

Buccal administration, where the tablet is placed between the cheek and gum, offers another alternative. This method is characterized by slower absorption over a more extended period, leading to sustained serum levels but lower peak concentrations compared to sublingual administration. gynuity.org Research comparing buccal and sublingual routes has shown that sublingual administration results in a significantly higher Cmax and AUC. The rate of buccal absorption is reported to be faster than vaginal dosing. nih.gov

Rectal Administration

Interactive Table: Pharmacokinetic Parameters of this compound by Administration Route

Diarrhea, Abdominal Pain, Nausea, Vomiting, Flatulence, Dyspepsia, Constipation

Diarrhea is frequently reported and is often the most common gastrointestinal side effect nih.govwikipedia.orgrxlist.comdrugs.comdroracle.ai. In clinical trials for the prevention of NSAID-induced gastric ulcers, the incidence of diarrhea at a dose of 800 mcg daily averaged 13%, ranging from 14-40% in controlled trials rxlist.compfizermedicalinformation.com. Diarrhea is dose-related and typically develops early in the course of therapy, often resolving within about 8 days wikipedia.orgrxlist.comdrugs.compfizermedicalinformation.com. In some cases (around 2% in clinical trials), it may necessitate discontinuation of the medication wikipedia.orgrxlist.comdrugs.compfizermedicalinformation.com. Rare instances of severe diarrhea leading to dehydration have been reported rxlist.compfizermedicalinformation.commedicalnewstoday.com.

Abdominal pain is another common gastrointestinal adverse effect nih.govrxlist.comdrugs.comdroracle.ai. In NSAID trials, abdominal pain occurred in 13-20% of patients, and in all studies, it was reported in about 7% of patients rxlist.compfizermedicalinformation.com. However, there was no consistent difference in incidence compared to placebo in these trials wikipedia.orgrxlist.compfizermedicalinformation.com.

Other reported gastrointestinal effects with incidences greater than 1% in clinical trials include nausea (3.2%), flatulence (2.9%), dyspepsia (2.0%), vomiting (1.3%), and constipation (1.1%) rxlist.comdroracle.aipfizermedicalinformation.com. Similar to abdominal pain, the incidence of these effects was not significantly different from placebo in clinical trials wikipedia.orgrxlist.compfizermedicalinformation.com.

Taking this compound with food can help minimize the incidence of diarrhea rxlist.comdrugs.compfizermedicalinformation.com. Coadministration with magnesium-containing antacids may increase the incidence of diarrhea and should be avoided nih.govrxlist.compfizermedicalinformation.com.

Note: Incidence rates are based on clinical trials for the prevention of NSAID-induced gastric ulcers unless otherwise specified. rxlist.compfizermedicalinformation.com

Uterine Hyperstimulation

Uterine hyperstimulation, characterized by excessive frequency or duration of uterine contractions, is a known risk associated with the use of uterotonic agents, including this compound wikipedia.orgpfizermedicalinformation.com. This can potentially compromise uteroplacental blood flow wikipedia.orgpfizermedicalinformation.com. The risk of uterine hyperstimulation is a concern when this compound is used for cervical ripening or labor induction wikipedia.orgpfizermedicalinformation.com. Some research suggests that this compound-induced hyperstimulation may be more challenging to manage compared to hyperstimulation caused by other agents wikipedia.org.

Post-Administration Bleeding and Cramping

Bleeding and cramping are commonly experienced following the administration of this compound, particularly when used for gynecological indications such as medical abortion or management of early pregnancy loss wikipedia.orgdroracle.aiaafp.org. This is a direct result of this compound's ability to induce uterine contractions hres.cawikipedia.orgdroracle.aiaafp.org. The bleeding can be heavier than typical menstrual bleeding wikipedia.orgaafp.org. While generally expected effects, excessive bleeding requiring medical attention is possible though uncommon droracle.ai. Cramping and bleeding typically commence within a few hours of administration and may persist for several days, with lighter bleeding potentially lasting longer aafp.org. In clinical trials for the prevention of NSAID-induced ulcers, gynecological disorders reported with incidences less than 1% included spotting (0.7%), cramps (0.6%), hypermenorrhea (0.5%), menstrual disorder (0.3%), and dysmenorrhea (0.1%) rxlist.compfizermedicalinformation.com. Postmenopausal vaginal bleeding has also been related to this compound administration rxlist.compfizermedicalinformation.com.

Headache

Headache is another adverse effect that has been reported in individuals using this compound. medscape.compfizermedicalinformation.comnih.govdroracle.ai In clinical trials, headache has been reported with varying frequencies. For example, in some trials, headache was reported by more than 1% of subjects receiving this compound, with an incidence of around 2.4%. pfizermedicalinformation.comdroracle.ai However, some studies have indicated that the incidence of headache in this compound groups was not significantly different compared to placebo groups. pfizermedicalinformation.com

In studies comparing this compound to other medications, such as oxytocin for postpartum hemorrhage prevention, headache was more commonly associated with the oxytocin group than the this compound group. scirp.org

Reported incidence rates of headache in clinical trials have included:

Note: Incidence rates can vary based on the specific study and patient population.