Alprostadil

Erectile dysfunction.

Erectile dysfunction (ED) is a common condition and can usually be managed pharmacologically, with drugs delivered by intracavernosal injection (ICI), transurethrally or orally. The cardiovascular status of the patient and his overall fitness for renewed sexual activity must be assessed before treatment for ED is initiated. The efficacy of sildenafil is related to the extent and severity of ED, and is significantly reduced in patients with severe vasculogenic ED, ED associated with diabetes and after radical prostatectomy. Alprostadil (prostaglandin E1) is the drug of first choice in patients treated with ICI; it is effective in 72.6% of men with ED and is associated with a low risk of priapism and cavernosal fibrosis. Transurethral alprostadil is significantly less effective than alprostadil ICI, producing improved erections in 30%-40%, but rigid erections in only 10%, of men with ED. There is Level II evidence that: alprostadil ICI is an effective treatment for ED papaverine ICI is associated with a high risk of cavernosal fibrosis and priapism papaverine ICI should be restricted to informed patients refractory to treatment with alprostadil ICI transurethral alprostadil is less effective than alprostadil ICI sildenafil is an effective treatment for ED.

Topiglan MacroChem.

MacroChem is developing Topiglan, a topical gel containing prostaglandin E1 (PGE1 or alprostadil) and its patented through-the-skin absorption enhancer excipient (SEPA), for the potential treatment of erectile dysfunction. By September 2000, it was in phase III clinical trials [382682]. By October 2000, MacroChem expected to file an NDA for Topiglan in late 2002 [387433]. In January 2002, at the JP Morgan Hambrecht & Quist 20th Annual Healthcare Conference in San Francisco, CA, MacroChem stated that further phase III studies were planned, including a reformulation that could reduce initation and increase dosage, as well as providing new packaging that improves dose consistency These studies should be underway by the third quarter of 2002, with a potential launch in late 2003 or early 2004 [436390]. The company's patented SEPA technology used in Topiglan is an absorption enhancer for transdermal delivery that has the potential to effectively increase the passage of therapeutic agents through the skin. The application of SEPA alone to the skin of carcinogenic-sensitive rats did not cause the development of tumors attributable to the SEPA [357621]. The company received a US notice of allowance of all patent claims covering Topiglan in February 1999. The patent (US-05942545) was issued in August 1999 [316028], [337720]. Further patent applications are pending in Canada, Europe and Japan [337720]. In February 2000, MacroChem filed further patent applications in 13 countries in Europe, Asia and Latin America and with the EPO [355947].

Intravenous prostaglandin E1 (alprostadil) bolus in ductus arteriosus-dependent CHD: valid or absolutely contraindicated?

The use of prostaglandin E1 is well documented in ductus arteriosus-dependent CHD or in neonatal pulmonary pathologies that cause severe pulmonary hypertension. The intravenous infusion is well established in loading infusion and maintenance with an onset of action of 30 minutes until 2 hours or even more. Our aim is to report three patients with pulmonary atresia that presented hypercyanotic spell due to a ductal spasm during cardiac catheterisation in whom the administration of a bolus of alprostadil reversed the spasm and increased pulmonary flow, immediately stabilising the condition of the patients allowing subsequent successful stent placement with no serious complications or sequelae after the administration of the bolus. More studies are needed to make a recommendation regarding the use of alprostadil in bolus in cases where the ductal spasm might jeopardise the life of the patient.

Alprostadil for the treatment of impotence.

Erectile dysfunction (ED) affects over 150 million men worldwide. Oral phosphodiesterase-5 (PDE5) inhibitors are currently used as a first-line therapy and a second-line therapy with either intracavernosal (Caverject) or intraurethral (MUSE) alprostadil is required for a few men who show poor response or intolerance to PDE5 inhibitors. This article reviews the pharmacology, pharmacokinetics, medical applications, efficacy and safety of alprostadil in the treatment of men with ED. The goal of this article is to review the currently published clinical data of alprostadil to establish its potential role in managing men, in particular, those who fail to respond to traditional PDE5 inhibitors. Relevant articles and abstracts were reviewed from PUBMED and conference proceedings. Alprostadil, a synthetic form of prostaglandin E1, is used as second-line therapy in managing men with ED. It has a unique role in men with ED secondary to diabetes and ED secondary to radical pelvic surgery (e.g., radical prostatectomy). In view of these new indications, the role of alprostadil is being redefined. Both intracavernosal and intraurethral alprostadil are approved for use in all countries, and following positive results from recent Phase III trials, topical alprostadil has gained approval in Canada.

Prostaglandin E1 inhibits endocytosis in the β-cell endocytosis.

Prostaglandins inhibit insulin secretion in a manner similar to that of norepinephrine (NE) and somatostatin. As NE inhibits endocytosis as well as exocytosis, we have now examined the modulation of endocytosis by prostaglandin E1 (PGE1). Endocytosis following exocytosis was recorded by whole-cell patch clamp capacitance measurements in INS-832/13 cells. Prolonged depolarizing pulses producing a high level of Ca(2+) influx were used to stimulate maximal exocytosis and to deplete the readily releasable pool (RRP) of granules. This high Ca(2+) influx eliminates the inhibitory effect of PGE1 on exocytosis and allows specific characterization of the inhibitory effect of PGE1 on the subsequent compensatory endocytosis. After stimulating exocytosis, endocytosis was apparent under control conditions but was inhibited by PGE1 in a Pertussis toxin-sensitive (PTX)-insensitive manner. Dialyzing a synthetic peptide mimicking the C-terminus of the α-subunit of the heterotrimeric G-protein Gz into the cells blocked the inhibition of endocytosis by PGE1, whereas a control-randomized peptide was without effect. These results demonstrate that PGE1 inhibits endocytosis and Gz mediates the inhibition.

Prostaglandin E1 and Its Analog Misoprostol Inhibit Human CML Stem Cell Self-Renewal via EP4 Receptor Activation and Repression of AP-1.

Effective treatment of chronic myelogenous leukemia (CML) largely depends on the eradication of CML leukemic stem cells (LSCs). We recently showed that CML LSCs depend on Tcf1 and Lef1 factors for self-renewal. Using a connectivity map, we identified prostaglandin E1 (PGE1) as a small molecule that partly elicited the gene expression changes in LSCs caused by Tcf1/Lef1 deficiency. Although it has little impact on normal hematopoiesis, we found that PGE1 treatment impaired the persistence and activity of LSCs in a pre-clinical murine CML model and a xenograft model of transplanted CML patient CD34+ stem/progenitor cells. Mechanistically, PGE1 acted on the EP4 receptor and repressed Fosb and Fos AP-1 factors in a β-catenin-independent manner. Misoprostol, an FDA-approved EP4 agonist, conferred similar protection against CML. These findings suggest that activation of this PGE1-EP4 pathway specifically targets CML LSCs and that the combination of PGE1/misoprostol with conventional tyrosine-kinase inhibitors could provide effective therapy for CML.

PGE1 Suppresses the Expression of M2 Markers on Macrophages Through Prostaglandin Receptors.

M2-like tumor-associated macrophages (TAMs) are a promising target for cancer immunotherapy, particularly for cancer patients who are refractory to current immune checkpoint inhibitors (ICIs). Previously, we showed that prostaglandin E1 (PGE1) enhances the expression of M1 markers, including HLA-DR, on macrophages and induces the M1 polarization of TAMs in vivo. This study investigated the pharmacological mechanisms by which PGE1 and its derivatives suppress the expression of M2 markers, including TREM2 and CXCR2. Macrophages were cultured in ultralow attachment dishes either alone or in combination with liver cancer cell lines to generate homospheroids or heterospheroids. Cell surface marker expression was assessed by flow cytometry. Compared with homospheroids, M2 marker expression on macrophages in heterospheroids was significantly increased, suggesting that heterospheroid culture promotes M2 polarization. PGE1 decreased M2 marker expression in heterospheroids more effectively compared with PGE2, PGE3, misoprostol, and 13,14-dihydro-15-keto-PGE1, whereas the suppressive effects of 15-keto- and 13,14-dihydro-PGE1s, and lubiprostone were comparable to that of PGE1. Pharmacological inhibition of prostaglandin receptors revealed that EP2 and EP4 receptors are involved in the PGE1-induced reprogramming of M2-like macrophages to M1 macrophages. In summary, PGE1 and its derivatives are promising TAM-targeting immunotherapeutics.

Prostaglandin E1: a review.

Work on the structure of prostaglandin E1 (PGE1), isolated from natural sources, was completed 25 years ago (1). Shortly after, methods for the chemical synthesis of PG with their natural configuration were developed in the laboratories of the UpJohn Company (2) and of E. J. Corey (3) and, by the late sixties, PGE1 became widely available. The information since accumulated about its biological and clinical effects is more substantial than for any other PG. This review will draw together some of this information, focusing on recent studies of its mechanisms of action.

Prostaglandin E1 Treatment for Lumbar Spinal Canal Stenosis: Review of the Literature.

The important pathophysiologic factor of neurogenic intermittent claudication (NIC) in lumbar spinal canal stenosis (LSCS) has been reported to be the reduction in intraneural blood flow and a state of relative ischemia in nerve tissues. Prostaglandin E1 (PGE1) presumably improves symptoms in patients with LSCS by improving the blood flow in the cauda equina and nerve roots through its vasodilation and antiplatelet aggregation effects. The purpose of the study was to summarize the results of previous studies regarding PGE1 treatment for LSCS and to describe the details of PGE1 treatment to all physicians who take care of patients with LSCS. Review of the literature. There are 3 PGE1-related products that have been used clinically for the treatment of LSCS: PGE1, lipo-PGE1, and limaprost (PGE1 derivative). Experimental studies have been performed to verify the efficacy of PGE1 treatment for LSCS. Many studies have reported clinical outcomes of PGE1 treatment in patients with LSCS. Overall, previous studies examining PGE1 treatment for LSCS demonstrate improvement in several clinical outcome measures such as the visual analog scale, Japanese Orthopaedic Association score, and NIC distance, although most of the studies have only short-term follow-up. Based on the results of previous studies, PGE1 treatment may be an option as a conservative treatment for LSCS. However, future studies with high-quality and long-term follow-up are necessary. Future studies also should include refinement of indications, administration period, as well as comparisons between PGE1 treatment and other conservative treatments such as epidural injection.

SOP conservative (medical and mechanical) treatment of erectile dysfunction.

Erectile dysfunction (ED) is the most frequently treated male sexual dysfunction worldwide. ED is a chronic condition that exerts a negative impact on male self-esteem and nearly all life domains including interpersonal, family, and business relationships. The aim of this study is to provide an updated overview on currently used and available conservative treatment options for ED with a special focus on their efficacy, tolerability, safety, merits, and limitations including the role of combination therapies for monotherapy failures. The methods used were PubMed and MEDLINE searches using the following keywords: ED, phosphodiesterase type 5 (PDE5) inhibitors, oral drug therapy, intracavernosal injection therapy, transurethral therapy, topical therapy, and vacuum-erection therapy/constriction devices. Additionally, expert opinions by the authors of this article are included. Level 1 evidence exists that changes in sedentary lifestyle with weight loss and optimal treatment of concomitant diseases/risk factors (e.g., diabetes, hypertension, and dyslipidemia) can either improve ED or add to the efficacy of ED-specific therapies, e.g., PDE5 inhibitors. Level 1 evidence also exists that treatment of hypogonadism with total testosterone < 300 ng/dL (10.4 nmol/L) can either improve ED or add to the efficacy of PDE5 inhibitors. There is level 1 evidence regarding the efficacy and safety of the following monotherapies in a spectrum-wide range of ED populations: PDE5 inhibitors, intracavernosal injection therapy with prostaglandin E1 (PGE1, synonymous alprostadil) or vasoactive intestinal peptide (VIP)/phentolamine, and transurethral PGE1 therapy. There is level 2 evidence regarding the efficacy and safety of the following ED treatments: vacuum-erection therapy in a wide range of ED populations, oral L-arginine (3-5 g), topical PGE1 in special ED populations, intracavernosal injection therapy with papaverine/phentolamine (bimix), or papaverine/phentolamine/PGE1 (trimix) combination mixtures. There is level 3 evidence regarding the efficacy and safety of oral yohimbine in nonorganic ED. There is level 3 evidence that combination therapies of PDE5 inhibitors + either transurethral or intracavernosal injection therapy generate better efficacy rates than either monotherapy alone. There is level 4 evidence showing enhanced efficacy with the combination of vacuum-erection therapy + either PDE5 inhibitor or transurethral PGE1 or intracavernosal injection therapy. There is level 5 evidence (expert opinion) that combination therapy of PDE5 inhibitors + L-arginine or daily dosing of tadalafil + short-acting PDE5 inhibitors pro re nata may rescue PDE5 inhibitor monotherapy failures. There is level 5 evidence (expert opinion) that adding either PDE5 inhibitors or transurethral PGE1 may improve outcome of penile prosthetic surgery regarding soft (cold) glans syndrome. There is level 5 evidence (expert opinion) that the combination of PDE5 inhibitors and dapoxetine is effective and safe in patients suffering from both ED and premature ejaculation.

Evaluation of alprostadil (prostaglandin E1) in the management of congenital heart disease in infancy.

Prostaglandins have been shown to relax the smooth muscle of the ductus arteriosus in the fetus in utero. This physiologic action has been applied to the management of newborn infants with certain types of congenital malformations. Infants with lesions producing right ventricular outflow obstruction have a compromised pulmonary circulation and require a patent ductus arteriosus for adequate pulmonary blood flow. Infusion of alprostadil (PGE1) dilates the ductus, increases pulmonary blood flow, and thereby improves oxygenation. Likewise, infants with aortic arch interruption or coarctation of the aorta are dependent on an open ductus to maintain lower body perfusion. Alprostadil is of great benefit in this situation as well. The side effects of alprostadil include peripheral vasodilation and hypotension and, most importantly, apnea. Hyperpyrexia and jitteriness may also occur. Side effects occur only in about 20% of infants and usually are easily reversed. The benefits therefore greatly outweigh the risks, but careful monitoring is essential.

Successful treatment of nonocclusive mesenteric ischemia after aortic valve replacement with continuous arterial alprostadil infusion: A case report.

Nonocclusive mesenteric ischemia (NOMI) after surgery has an extremely poor prognosis with a mortality rate of 30-100%. We report a patient with NOMI following aortic valve replacement who failed to improve despite continuous intra-arterial infusion of papaverine, but was successfully treated with alprostadil (prostaglandin E1 [PGE1]) infusion. The patient is a 77-year-old man who underwent aortic valve replacement. Due to elevated serum lactate levels five hours after intensive care unit admission, superior mesenteric arteriography was performed, establishing the diagnosis of NOMI. Although continuous intra-arterial infusion of papaverine was begun, lactate levels remained elevated. Repeat angiography and laparotomy revealed extensive ischemic changes of the intestine. The vasodilator was changed to PGE1, which improved arterial spasm. The patient ultimately needed an ileocecal resection, but the extent of the resection was limited with concomitant PGE1 administration. In the present patient, although NOMI was unresponsive to appropriate treatment including intra-arterial infusion of papaverine, continuous intra-arterial infusion of PGE1 salvaged most of the intestine. In a patient with recurrent NOMI despite appropriate treatment including intra-arterial infusion of papaverine, continuous intra-arterial infusion of PGE1 may limit the extent of intestinal resection needed. Continuous intra-arterial infusion of PGE1 may be a useful treatment for patients with refractory NOMI.

Prostaglandin E1 attenuates AngII-induced cardiac hypertrophy via EP3 receptor activation and Netrin-1upregulation.

Pathological cardiac hypertrophy induced by activation of the renin-angiotensin-aldosterone system (RAAS) is one of the leading causes of heart failure. However, in current clinical practice, the strategy for targeting the RAAS is not sufficient to reverse hypertrophy. Here, we investigated the effect of prostaglandin E1 (PGE1) on angiotensin II (AngII)-induced cardiac hypertrophy and potential molecular mechanisms underlying the effect. Adult male C57 mice were continuously infused with AngII or saline and treated daily with PGE1 or vehicle for two weeks. Neonatal rat cardiomyocytes were cultured to detect AngII-induced hypertrophic responses. We found that PGE1 ameliorated AngII-induced cardiac hypertrophy both in vivo and in vitro. The RNA sequencing (RNA-seq) and expression pattern analysis results suggest that Netrin-1 (Ntn1) is the specific target gene of PGE1. The protective effect of PGE1 was eliminated after knockdown of Ntn1. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the PGE1-mediated signaling pathway changes are associated with the mitogen-activated protein kinase (MAPK) pathway. PGE1 suppressed AngII-induced activation of the MAPK signaling pathway, and such an effect was attenuated by Ntn1 knockdown. Blockade of MAPK signaling rescued the phenotype of cardiomyocytes caused by Ntn1 knockdown, indicating that MAPK signaling may act as the downstream effector of Ntn1. Furthermore, inhibition of the E-prostanoid (EP) 3 receptor, as opposed to the EP1, EP2, or EP4 receptor, in cardiomyocytes reversed the effect of PGE1, and activation of EP3 by sulprostone, a specific agonist, mimicked the effect of PGE1. In conclusion, PGE1 ameliorates AngII-induced cardiac hypertrophy through activation of the EP3 receptor and upregulation of Ntn1, which inhibits the downstream MAPK signaling pathway. Thus, targeting EP3, as well as the Ntn1-MAPK axis, may represent a novel approach for treating pathological cardiac hypertrophy.

Prostaglandin E1 administration post liver transplantation and renal outcomes: A retrospective single center experience.

Prostaglandin E1 (PGE1), or alprostadil, is a potent vasodilator that improves hepatic blood flow and reduces ischemia-reperfusion injury post-liver transplantation (LT). However, the benefits of PGE1 on renal function after LT have not yet been well described. To assess the impact of PGE1 administration on renal function in patients who underwent liver or liver-kidney transplant. This retrospective study included all patients who underwent liver or liver-kidney transplant at our institution from January, 2011 to December, 2021. Patients were classified based on whether they received PGE1. PGE1 was administered post-LT to those with transaminases > 1000 U/L in the immediate postoperative period. Demographics, post-LT treatments and/or complications, renal function, and survival were analyzed. Multivariable logistic regression analysis was performed, and a two-tailed P value < 0.05 was considered statistically significant. A total of 145 patients underwent LT, with 44 (30%) receiving PGE1. Baseline patient characteristics were comparable, except the PGE1 group had significantly higher aspartate aminotransferase (AST) (1961.9 U/L &#xb1; 1862.3 U/L vs 878 U/L &#xb1; 741.4 U/L, P = 0.000), alanine aminotransferase (1070.6 U/L &#xb1; 895 U/L vs 547.7 U/L &#xb1; 410 U/L, P = 0.000), international normalized ratio on post-LT day 1 (2 &#xb1; 0.74 vs 1.8 &#xb1; 0.4, P = 0.03), a longer intensive care unit stay (8.1 days &#xb1; 11.8 days vs 3.8 days &#xb1; 4.6 days, P = 0.003), more vasopressor use (55.53 hours &#xb1; 111 hours vs 16.33 hours &#xb1; 26.3 hours, P = 0.002), and higher immediate postoperative complications (18.6% vs 4.9%, P = 0.04). The PGE1 group also had a significantly higher 90-day readmission rate (29.6% vs 13.1%, P = 0.02) and lower 1-year liver graft survival (87.5% vs 98.9%, P = 0.005). However, 30-day readmission (31.6% vs 27.4%, P = 0.64), LT complications (hepatic artery thrombosis, biliary complications, rejection of liver graft, cardiomyopathy), 1-year patient survival (96.9% vs 97.8%, P = 0.77), overall liver graft survival, and overall patient survival were similar between the two groups (95.4% vs 93.9%, P = 0.74 and 88.4% vs 86.9%, P = 0.81 respectively). Although the PGE1 group had a significantly lower glomerular filtration rate (eGFR) on post-LT day 7 (46.3 mL/minute &#xb1; 26.7 mL/minute vs 62.5 mL/minute &#xb1; 34 mL/minute, P = 0.009), the eventual need for renal replacement therapy (13.6% vs 5.9%, P = 0.09), the number of dialysis sessions (0.91 vs 0.27, P = 0.13), and eGFR at 1-month (37.2 mL/minute &#xb1; 35.9 mL/minute vs 42 mL/minute &#xb1; 36.9 mL/minute, P = 0.49), 6-months (54.8 mL/minute &#xb1; 21.6 mL/minute vs 62 mL/minute &#xb1; 21.4 mL/minute, P = 0.09), and 12-months (63.7 mL/minute &#xb1; 20.7 mL/minute vs 62.8 mL/minute &#xb1; 20.3 mL/minute, P = 0.85) post-LT were similar to those in the non-PGE1 group. In patients who received PGE1 for ischemia-reperfusion injury, despite immediate acute renal injury post-LT, the renal function at 1-month, 6-months, and 12-months post-LT was similar compared to those without ischemia-reperfusion injury. Prospective clinical trials are needed to further elucidate the benefits of PGE1 use in renal function.

A comparison of some pharmacological actions of prostaglandin E1, 6-oxo-PGE1 and PGI2.

Some pharmacological actions of prostaglandin E1 (PGE1), 6-oxo-PGE1 and PGI2 have been studied. 6-oxo-PGE1 and PGE1 relaxed guinea-pig tracheal muscle in vitro and increased nasal patency in normal volunteers and in subjects with vasomotor rhinitis whereas PGI2 produced opposite effects. All three compounds produced bronchodilatation in the anaesthetised guinea-pig and relaxed human respiratory tract muscle in vitro. PGI2 was several times more potent than either 6-oxo-PGE1 or PGE1 against ADP-induced aggregation of human and baboon platelets in vitro. Intravenous 6-oxo-PGE1 in the baboon caused an ex vivo inhibition of platelet aggregation, but the EC50 was 7.7 times that of PGI2. As a vasodepressor in the baboon 6-oxo-PGE1 and PGI2 were equipotent. Thus with the exception of the vasodepressor effect, the actions of 6-oxo-PGE1 qualitatively and quantitatively resembled those of the structurally related PGE1 rather than those of PGI2.

Clinical application of prostaglandin E1 (PGE1) upon orthodontic tooth movement.

Chemically produced prostaglandin E1 (PGE1) was administered in clinical cases of orthodontic tooth movement. In the first phase, lingual arch springs were applied on both sides of the maxilla to upper first premolars which were scheduled for extraction. One side received submucosal injections of PGE1 and the other received vehicle injections. The rate of tooth movement in the buccal direction approximately doubled on the side of several PGE1 injections as compared to the control side. In the second phase, the PGE1 injections were applied in canine-retraction cases for up to 3 weeks in first-premolar-extraction cases. The rate of distal canine movement was almost double on the side receiving PGE1 injections as compared to the vehicle-injected side. In the third phase, the PGE1 injections were applied on routine canine retraction in first-premolar-extraction cases. The rate of distal canine movement was almost 1.6-fold on the side of PGE1 injections as compared to the vehicle-injected side. Throughout this study, no side effects were observed macroscopically in the gingiva and roentgenographically in the alveolar bone, except for a slight pain reaction consistent with orthodontic tooth movement.

Prostaglandin E1 incorporated in lipid microspheres (lipo PGE1).

Prostaglandin E1 (PGE1) was incorporated into soybean oil microspheres 0.2 micron in diameter, using lecithin as surfactant. The pharmacological effects of this new galenic form of PGE1 (lipo PGE1) was evaluated in experimental peripheral arterial occlusive disease in rats and in an ex vivo antithrombosis test in rats. It was shown in the experiments that lipo PGE1 had a more marked protective effect in arterial occlusive tissue injury caused by lauric acid and a more potent platelet aggregation inhibitory effect than PGE1. Total radioisotope activity of 3H-PGE1 in lipid microspheres in blood was higher and persisted longer than that of PGE1 in rats. These results suggested that the favourable features of lipo PGE1 depended on protection against inactivation in the lung and its targeting effect to tissues injured by arterial occlusion.

Prostaglandin E1 hyperthermia in water or food deprived rats.

The effect of 48 hours of water deprivation on the colonic temperature response to intrahypothalamic injection of prostaglandin E1 (PGE1) was investigated in adult male rats. Water deprivation did not alter colonic temperature of rats at a neutral ambient temperature. Administration of PGE1 at doses of 50, 200 and 400 ng gave rise to a short latency dose dependent hyperthermia in both control and water deprived rats. Water deprived rats had significantly greater increases in colonic temperature following the two higher doses of PGE1. Control rats and water deprived rats exposed to the cold (5 degrees C) had decreases in colonic temperature which were not significantly different. Water deprivation, which should increase the plasma levels of the putative endogenous antipyretic vasopressin, does not attenuate PGE1 hyperthermia but has a slight enhancing effect. Following food deprivation for 48 hours rats had a slight but significantly greater increase in colonic temperature following intrahypothalamic injection of 200 ng PGE1. Thus the water deprivation induced change in responsiveness to PGE1 may be due to the decrease in food intake which accompanies water deprivation. The mechanism by which rats exhibit an enhanced febrile response to PGE1 administration following food or water deprivation is not yet known.

Ocular and optic nerve ischemia: recognition and treatment with intravenous prostaglandin E1.

Ischemia of the optic nerve, the retina and the choroid are common problems in ophthalmology. This paper presents the different types of ischemia and their treatment with prostaglandin E1 (PGE1), a powerful vasodilator of the microcirculation. This is a review article of various previously published case reports and studies presenting patients with different types of ocular and optic nerve ischemia. Their treatment with intravenous (IV) PGE1 is described. Treatment for acute and chronic problems is presented. The visual acuity and/or the visual fields improved in almost all the treated patients. When measured, the blood flow velocities also improved. No complications due to the use of PGE1 were seen. Treatment with IV PGE1 should be considered in cases of ocular and optic nerve ischemia to immediately restore blood flow to these structures and improve the visual acuity. Intravenous prostaglandin E1 is an effective treatment for ocular and optic nerve ischemia leading to immediate visual improvement.

Prostaglandins as a Topical Therapy for Erectile Dysfunction: A Comprehensive Review.

Erectile dysfunction (ED) is a substantial cause of dissatisfaction among many men. This discontentment has led to the emergence of various drug treatment options for this problem. Unfortunately, due to various interactions, contraindications, and side effects, systemic therapies such as phosphodiesterase-5 inhibitors (including sildenafil, tadalafil, vardenafil, avanafil, etc.) are not welcomed in many patients. These problems have led researchers to look for other ways to reduce these complications. This article holistically reviews the efficacy of topical prostaglandins and their role in treating ED. We sought to provide a comprehensive overview of recent findings on the current topic by using the extensive literature search to identify the latest scientific reports on the topic. In this regard, topical and transdermal treatments can be suitable alternatives. In diverse studies, prostaglandins, remarkably PGE1 (also known as alprostadil), have been suggested to be an acceptable candidate for topical treatment. Numerous formulations of PGE1 have been used to treat patients so far. Still, in general, with the evolution of classical formulation methods toward modern techniques (such as using nanocarriers and skin permeability enhancers), the probability of treatment success also increases. Hamzehnejadi M, Tavakoli MR, Homayoun F et al. Prostaglandins as a Topical Therapy for Erectile Dysfunction: A Comprehensive Review. Sex Med Rev 2022;10:764-781.

The rationale for prostaglandin E1 in erectile failure: a survey of worldwide experience.

Prostaglandin E1 (PGE1, alprostadil) is used worldwide for self-injection therapy in erectile failure and was recently officially approved for this purpose in the United States and most European countries. Therefore a comprehensive overview on biochemistry, pharmacology and therapeutic results of PGE1 is provided. The relevant literature on PGE1 was reviewed along with personal experience with 4,577 patients during a 7-year period. PGE1 was compared to other vasoactive drugs, such as papaverine, the mixture of papaverine and phentolamine or linsidomine alone. In Europe PGE1 was officially approved for the therapy of peripheral arterial occlusive disease of the lower limbs in 1984. The drug has direct relaxing effects on smooth muscle cells of vessels and cavernous bodies, shows inhibitory effects on platelet aggregation, on low-density lipoprotein entry into the vascular wall and on presynaptic noradrenaline release and, therefore, it prevents the progress of atherosclerosis. In erectile failure PGE1 shows a response rate of more than 70% and, compared to papaverine with phentolamine, a considerably lower risk of priapism (0.35% versus 6%, respectively) as well as of local fibrotic complications. Except for rare cases of blood pressure decrease, no systemic side effects were observed after intracavernous injection of PGE1. For self-injection therapy, PGE1 presently represents the most efficacious and safest drug. Ongoing trials with topical and especially intraurethral PGE1 are promising and may offer less invasive therapies in the near future.

Developmental Differences in Platelet Inhibition Response to Prostaglandin E1.

The mechanisms underlying neonatal platelets hyporesponsiveness are not fully understood. While previous studies have demonstrated developmental impairment of agonist-induced platelet activation, differences in inhibitory signaling pathways have been scarcely investigated. To compare neonatal and adult platelets with regard to inhibition of platelet reactivity by prostaglandin E1 (PGE1). Platelet-rich plasma from umbilical cord (CB) or adult blood was incubated with PGE1 (0-1 &#x3bc;M). We assessed aggregation in response to adenosine diphosphate (ADP), collagen, and thrombin receptor activating peptide as well as cyclic adenosine 3'5'-monophosphate (cAMP) levels (ELISA). G&#x3b1;s, G&#x3b1;i2, and total- and phospho-protein kinase A (PKA) were evaluated in adult and CB ultrapure and washed platelets, respectively, by immunoblotting. Neonatal (vs. adult) platelets display hypersensitivity to inhibition by PGE1 of platelet aggregation induced by ADP and collagen (PGE1 IC50: 14 and 117 nM for ADP and collagen, respectively, vs. 149 and 491 nM in adults). They also show increased basal and PGE1-induced cAMP levels. Mechanistically, PGE1 acts by binding to the prostanoid receptor IP (prostacyclin receptor), which couples to the G&#x3b1;s protein-adenylate cyclase axis and increases intracellular levels of cAMP. cAMP activates PKA, which phosphorylates different target inhibitor proteins. Neonatal platelets showed higher basal and PGE1-induced cAMP levels, higher G&#x3b1;s protein expression, and a trend to increased PKA-dependent protein phosphorylation compared to adult platelets. Neonatal platelets have a functionally increased PGE1-cAMP-PKA axis. This finding supports a downregulation of inhibitory when going from neonate to adult contributing to neonatal platelet hyporesponsiveness.

Cutaneous eruption in neonate with congenital heart defect.

Effects of lipo-prostaglandin E1 on wound bed microcirculation.

Lipo-prostaglandin E1 (lipo-PGE1) is a well-known potent vasodilator that increases peripheral blood flow. However, the effects of this agent on wound bed microcirculation still remain unclear. The present study aims to improve the experimental model which our group developed to visualise wound bed microcirculation and to evaluate acute stimulation by lipo-PGE1. The superficial stratum of the Wistar rat's ear skin was microsurgically excised preserving the subdermal vascular plexus. The preserved vessels, the wound bed microcirculation, were visualised under an intravital microscope-video-computer system. Animals were divided into three groups, a control group in which animals received vehicle control, a medium-dose group (6 &#x3bc;g/2 ml/kg lipo-PGE1) and a high-dose group (10 &#x3bc;g/2 ml/kg lipo-PGE1). The blood velocity and diameter of individual venules were measured from the recorded microcirculatory images, and the blood flow of the venule in the wound bed was evaluated. A significant increase in the wound bed blood flow was seen 10 minutes after lipo-PGE1 injection (p<0.05). This was approximately fourfold the baseline values. The increase was greatest in the medium-dose group. Extravasation and accumulation of lipo-PGE1 in the wound bed was observed. Lipo-PGE1 effectively increased wound bed microcirculation blood flow at the optimal dose. There is no conflict of interest.

Efficacy and Safety of Alprostadil in Microcirculatory Disturbances During Emergency PCI: A Meta-Analysis of Randomized Controlled Trials.

The clinical advantage of alprostadil [prostaglandin E1 (PGE1)] in the treatment of microcirculatory disturbances (defined as no-reflow or slow-flow) in acute percutaneous coronary intervention (PCI) is still disputed. The purpose of our study was to review the efficacy of PGE1 supplements in patients with acute myocardial infarction (AMI) who had urgent PCI. This study was a meta-analysis of randomized controlled trials. PubMed, Embase, the Cochrane Library, Ovid, ProQuest, Scopus, the Chinese BioMedical Literature Database, China National Knowledge Internet, the China Science and Technology Journal Database, and the Wanfang Data Knowledge Service Platform were used as sources. We included randomized controlled trials including PGE1 for the treatment of intraoperative microcirculatory disorders and major cardiovascular adverse events in emergency PCI in people with AMI. Independent data extraction was conducted, and study quality was assessed. The meta-analysis was carried out by using random effects models to calculate the risk ratio (RR) of microcirculatory disorders between groups receiving PGE1 and those receiving placebo, nitroglycerin, or tirofiban. The primary endpoint of the study was the incidence of microcirculatory disturbances. Secondary outcomes included corrected thrombolysis in myocardial infarction (TIMI) frame count (cTFC), the percentage of patients with TIMI myocardial perfusion grade 3 (TMPG3), and the percentage of patients with myocardial blush grade 3 (MBG3) as efficacy indicators. Additionally, major adverse cardiovascular events (MACE) at 30 days and 180 days were assessed as safety indicators. There were 18 trials involving a total of 1458 participants. PGE1 significantly reduced the occurrence of microcirculation disorders compared with conventional medications and placebo [risk ratio 0.48, 95% confidence interval (CI) 0.36-0.63, I2 = 46%; cTFC (RR -4.74, 95% -6.85 to -2.63, I2 93%); percentage of patients with TMPG3 (RR 1.34, 95% CI 1.07-1.68, I2 70%) or MBG3 (RR 1.33, 95% CI 1.19-1.49, I2 0%); major adverse cardiovascular events (MACEs) in 30 days (RR 0.48, 95% CI 0.27-0.86, I2 0%); and MACEs in 180 days (RR 0.41, 95% CI 0.28-0.60, I2 0%)]. We found that&#xa0;PGE1 decreased the occurrence of micro-circulation disturbance in AMI and enhanced the outcome of PCI.&#xa0;Additional studies should be conducted to confirm these findings.

Prostaglandin E1 restores endothelial progenitor cell function in systemic sclerosis.

SSc is a chronic autoimmune disease characterized by microvascular injury and impaired angiogenesis, with endothelial progenitor cells (EPCs) playing a key role in vascular repair. EPC subsets, including endothelial colony-forming cells (ECFCs) and colony-forming unit-endothelial cells (CFU-ECs), are known to be dysfunctional in SSc, contributing to disease-associated vasculopathy. Prostaglandin E1 (PGE1) is a vasodilator with potential pro-angiogenic effects, but its impact on EPC numbers and function in SSc remains unexplored. This study aimed to investigate whether PGE1 treatment can modulate EPC numbers, specifically CFU-ECs and ECFCs, in patients with SSc and RP, and evaluate its potential role in promoting vascular repair. This study evaluated the effect of PGE1 on EPC levels in 12 SSc patients with RP and five healthy controls (HCs). CFU-EC and ECFC clusters were quantified before and after PGE1 treatment using standardized culture methods. PGE1 was administered intravenously over 8-9&#x2009;days. Statistical analyses compared EPC counts between the groups and time points. Baseline CFU-EC and ECFC cluster counts were significantly reduced in SSc patients compared with HCs (P&#x2009;=&#x2009;0.02 and P&#x2009;<&#x2009;0.01, respectively). Following PGE1 treatment, both CFU-EC and ECFC clusters significantly increased in SSc patients (P&#x2009;=&#x2009;0.02 and P&#x2009;=&#x2009;0.001, respectively), reaching levels comparable to HCs. No significant changes were observed in HCs across two time points. A significant delta in cluster counts was observed in SSc patients vs. HCs (CFU-EC: P&#x2009;=&#x2009;0.03; ECFC: P&#x2009;=&#x2009;0.01). PGE1 treatment restores CFU-EC and ECFC levels in SSc patients, suggesting a potential role in repairing vascular damage. These findings highlight PGE1's therapeutic benefits beyond vasodilation, supporting its use in SSc-associated microvasculopathy.

Could Lipo-Prostaglandin E1 Be the Key to Improving Success Rates in Free-Flap Microsurgery? A Systematic Review.

Background: Microsurgery and free tissue transfer with microanastomoses are common practices that are reliable for restoring anatomical function and/or morphology. Maintaining adequate blood flow to transferred tissue and preventing thrombosis are key challenges in improving the success of surgery. We conducted a systematic review to investigate the use, effects, and efficacy of lipo-prostaglandin E1 (lipo-PGE1) and PGE1, which have vasodilatory and anticoagulation effects, in microsurgery. Methods: Studies were reviewed for information about the administration of lipo-PGE1/PGE1, including the purpose, effectiveness, administered doses, and duration of use. This review included articles published up to 2024. Databases: PubMed, MEDLINE, and Embase were searched using the keywords: "flap" AND "prostaglandin E1" and "microsurgery" AND "prostaglandin E1." Results: The initial database search yielded 359 citations; 14 were included in our study with qualitative analysis. These 14 original articles reported PGE1/lipo-PGE1 use in microsurgery for the reconstruction of different anatomical sites, with the most common being the head and neck. Twenty-one different flaps were used; the most common flaps used in head, neck, and lower limb reconstructions were anterolateral thigh flaps. Most studies reported using PGE1/lipo-PGE1 as an antithrombotic, an anticoagulant, a vasodilator, and a strategy to examine blood flow post administration. Only one study compared its effectiveness between two groups and showed significantly lower perfusion-related complications in the prostaglandin group than in the control group. Conclusions: Lipo-PGE1/PGE1 has potential vasodilator effects that increase blood flow through free flaps and potential anticoagulant properties that help prevent thrombosis in microanastomoses. However, multicenter, randomized controlled studies are needed to fully elucidate its benefits.

Local cerebral blood flow with prostaglandin E1 or trimethaphan during cerebral aneurysm clip ligation.

This study was performed to examine changes in local cerebral blood flow during hypotensive anaesthesia with either prostaglandin E1 (PGE1) or trimethaphan (TMP). Local cerebral blood flow (LCBF), mean blood pressure (MBP), heart rate (HR), and hourly urine output (UO) were studied in 51 patients undergoing cerebral aneurysm surgery with neuroleptanalgesia (NLA). The incidence of vasospasm after aneurysm surgery, and outcome (Glasgow Outcome Scale) at discharge were evaluated. Measurements of LCBF were made using a thermal gradient blood flow meter. The dose of PGE1 or TMP was adjusted to maintain MBP at about 70 mmHg, and LCBF was studied during and after PGE1 or TMP administration. Hypotensive drugs were discontinued at the completion of aneurysm clipping. After starting PGE1 or TMP, MBP decreased immediately, but HR did not change in either group. The LCBF decreased 30 min after the start of TMP administration and increased immediately after its discontinuation, whereas PGE1 did not affect LCBF. Urine output increased during PGE1 administration but was unchanged during TMP. Neither drug affected surgical outcome or the incidence of vasospasm. These results suggest that PGE1 may be preferable to trimethaphan for hypotensive anaesthesia in cerebral aneurysm surgery because LCBF is maintained.

Prostaglandin E1 protects cardiomyocytes against hypoxia-reperfusion induced injury via the miR-21-5p/FASLG axis.

Prostaglandin-E1 (PGE1) is a potent vasodilator with anti-inflammatory and antiplatelet effects. However, the mechanism by which PGE1 contributes to the amelioration of cardiac injury remains unclear. The present study was designed to investigate how PGE1 protects against hypoxia/reoxygenation (H/R)-induced injuries by regulating microRNA-21-5p (miR-21-5p) and fas ligand (FASLG). Rat H9C2 cells and isolated primary cardiomyocytes were cultured under hypoxic conditions for 6 h (6H, hypoxia for 6 h), and reoxygenated for periods of 6 (6R, reoxygenation for 6 h), 12, and 24 h, respectively. Cells from the 6H/6R group were treated with various doses of PGE1; after which, their levels of viability and apoptosis were detected. The 6H/6R treatment regimen induced the maximum level of H9C2 cell apoptosis, which was accompanied by the highest levels of Bcl-2-associated X protein (Bax) and cleaved-caspase-3 expression and the lowest level of B-cell lymphoma 2 (Bcl-2) expression. Treatment with PGE1 significantly diminished the cell cytotoxicity and apoptosis induced by the 6H/6R regimen, and also decreased expression of IL-2, IL-6, P-p65, TNF-&#x3b1;, and cleaved-caspase-3. In addition, we proved that PGE1 up-regulated miR-21-5p expression in rat cardiomyocytes exposed to conditions that produce H/R injury. FASLG was a direct target of miR-21-5p, and PGE1 reduced the ability of H/R-injured rat cardiomyocytes to undergo apoptosis by affecting the miR-21-5p/FASLG axis. In addition, we proved that PGE1 could protect primary cardiomyocytes against H/R-induced injuries. These results indicate that PGE1 exerts cardioprotective effects in H9C2 cells during H/R by regulating the miR-21-5p/FASLG axis.

Shelf-life determination of prostaglandin E1 injections.

A rapid stability indicating assay for the determination of prostaglandin E1 (PGE1) in pharmaceuticals was developed using High Pressure Liquid Chromatography (HPLC). A solution of 20 micrograms/ml PGE1 in 4% alcohol and 0.9% saline has an activation energy of 18,683 cal/mol and the predicted shelf-lives were: at 4 degrees C t95 = 51.8 days and t90 = 106.5 days and at 25 degrees C t95 = 4.8 days and t90 = 9.8 days.

Intra-arterial alprostadil for nonatherosclerotic vasculopathy.

A 33-year-old man with a nonatherosclerotic vasculopathy of undetermined origin had progressive occlusive disease of the lower limb vessels. The resultant severe rest pain and ischemic ulceration of his foot were inoperable and unresponsive to conventional drug therapy. Treatment was begun with intra-arterially administered alprostadil (prostaglandin E1), a vasodilator and inhibitor of platelet aggregation. Although immediate benefit was equivocal, his rest pain had disappeared six weeks after infusion, and the ischemic ulcer almost healed completely. Blood flow studies showed increased flow to the feet, consistent with the subjective improvement. The beneficial effect of alprostadil suggests that further studies with this agent are warranted for patients with nonatherosclerotic vasculopathy.

Prostaglandin E1 in hand angiography.

Prostaglandin E1 (PGE1) is a rapid, potent vasodilator which, when infused into the arterial system in low doses by bolus injection, has no significant systemic effects and has a relatively long duration of action. Sixty-three hand angiograms were done on 55 patients, comparing PGE1 to tolazoline and to angiograms done with no vasodilation. There was no significant difference between PGE1 and tolazoline in digital artery opacification; however, venous opacification was very significantly better with PGE1. PGE1 should be a drug of choice in hand angiography.

Intravenous alprostadil, an analog of prostaglandin E1, prevents thiamylal-fentanyl-induced bronchoconstriction in humans.

Prostaglandin (PG) E(1) relaxes airway smooth muscle in animals. However, no clinical data have been published on the bronchorelaxant effects of IV alprostadil, an analog of PGE(1). We have described experimental thiamylal-fentanyl-induced bronchoconstriction in humans; we now report the effect of IV alprostadil on thiamylal-fentanyl-induced bronchoconstriction. Thirty-two patients were allocated randomly to a control group (n = 16) and alprostadil group (n = 16). Anesthesia was induced with thiamylal 5 mg/kg and vecuronium 0.3 mg/kg and maintained with a continuous infusion of thiamylal 15 mg. kg(-1). h(-1). The lungs of the patients were ventilated with 50% nitrous oxide in oxygen. Twenty minutes after the induction of anesthesia, patients in the control group were given a continuous infusion of normal saline 20 mL/h, and those in the alprostadil group received a continuous infusion of alprostadil 0.2 micro g. kg(-1). min(-1) (20 mL/h), both for 60 min. Both groups were then given fentanyl 5 micro g/kg. Systolic and diastolic arterial blood pressure, heart rate, mean airway resistance (Rawm), expiratory airway resistance (Rawe), and dynamic lung compliance (Cdyn) were measured at the baseline, just before the fentanyl injection (T30), at three consecutive 6-min intervals after fentanyl injection (T36, T42, and T48), and 30 min after fentanyl injection (T60). Baseline Rawm, Rawe, and Cdyn values were comparable between groups. In the control group, both Rawm and Rawe were significantly increased at T36-60, and Cdyn was significantly decreased at T36-60 compared with the baseline. Patients given alprostadil showed no change in Rawm, Rawe, or Cdyn at T36-60. Thus, IV alprostadil seems to have a bronchodilator effect in humans. IV alprostadil, an analog of prostaglandin E(1), prevents thiamylal-fentanyl-induced bronchoconstriction in humans. This finding suggests that IV alprostadil has a bronchodilator effect.

Interaction of receptors for prostaglandin E1/prostacyclin and insulin in human erythrocytes and platelets.

Prostaglandin E1/I2 and insulin receptors of human erythrocyte and platelet are capable of modulating each other's activity. This modulation of the receptor activity and number in one system by a second receptor system in human platelet and erythrocyte seems to be beneficial. Insulin increases the PGE1 binding to platelets and thereby enhances the platelet antiaggregatory action of prostaglandin by increasing cyclic AMP levels. Similarly, PGE1 increases insulin binding to human erythrocyte, and thereby reduces the optimum concentration of insulin for a maximal reduction in membrane microviscosity. During ischemia the reduced response of platelets to the inhibitory effect of PGE1 or PGI2 relates to the impaired PGE1/I2 receptor activity. Treatment of these platelets with insulin at physiological concentrations can normalise the PGE1/I2 receptor activity. This review focuses on the relationship between the two receptor systems in human blood cells.

Prostaglandin E1 treatment of congenital heart disease: use prior to neonatal transport.

Prostaglandin E1 (PGE1) is used to maintain the patency of the ductus arteriosus in neonates when it is necessary to circumvent a defect in the heart or aorta in order to provide adequate peripheral perfusion. It has recently been recommended that medical stabilization with PGE1 be done as soon as a ductus-dependent cardiac defect is suspected, preferably prior to transport of the infant to a tertiary care center for surgical repair of the defect. To accomplish this, hospitals providing obstetric services will need to maintain a supply of PGE1. This commentary provides guidelines for determining the need to stock PGE1 and presents a brief review of the physiology of the ductus arteriosus and the pharmacology and adverse effects of PGE1 therapy.

Effect of prostaglandin-E1 treatment on pyloric wall thickness in newborns with ductal-dependent critical congenital heart diseases.

Prostaglandin E1 (PGE1) is used in the medical treatment of ductal-dependent critical congenital heart disease (CCHD) in neonates. Apnea/bradycardia, hypotension, hypokalemia, and fever are the most important side effects of PGE1. Moreover, gastric outlet obstruction has been reported in a few case reports. A prospective study was conducted to investigate the effect of PGE1 treatment on pyloric wall thickness in newborns with congenital heart diseases. A total of 22 newborns with ductal-dependent CCHD having PGE1 infusion longer than a week were included in this study. Ultrasonographic measurements were performed before and one week after the PGE1 infusion to evaluate the pyloric thickness and length. The protocol was registered with ClinicalTrials.govidentifier NCT04496050. A total of 22 neonates with mean gestational age 38&#x2009;&#xb1;&#x2009;1.8&#xa0;weeks and birth weight 3105&#x2009;&#xb1;&#x2009;611 gr were enrolled in the study. The median time of the second ultrasound was seven days. The median cumulative dose of PGE1 given during this period was 108 mcg/kg/min. There was a statistically significant increase in post-treatment pyloric thickness and length compared to pre-treatment measurements (p&#x2009;<&#x2009;0.001, p&#x2009;<&#x2009;0.001). None of the patients with increased thickness and pyloric muscle length presented any symptoms. PGE1 treatment significantly increased the pyloric thickness and length after at least one-week treatment. PGE1 with its action mechanism is likely to cause gastric outlet obstruction, although not exactly pyloric stenosis on the condition used for a long time.

Cumulative Dose of Prostaglandin E1 Determines Gastrointestinal Adverse Effects in Term and Near-Term Neonates Awaiting Cardiac Surgery: A Retrospective Cohort Study.

This study aimed to assess the association between treatment characteristics of prostaglandin E1 including initiation time and duration, maximal and cumulative doses, and adverse effects. A retrospective cohort study in which medical records of neonates with duct-dependent lesions were studied for treatment parameters and adverse effects. Multivariable logistic regression model was applied for testing the effect PGE1 variables on outcomes. The primary outcomes of this study were association of adverse effects of PGE1 treatment with maximal dose, cumulative dose, and treatment duration. The secondary outcomes included safety of feeding in infants treated with PGE1. Eighty-two infants with duct-dependent lesions receiving PGE1 were included. Several infants who received early PGE1 treatment required ventilation support. Feeds were ceased more often as the cumulative dose and duration of PGE1 treatment increased. Gastrointestinal adverse effects were significantly associated with the cumulative dose of PGE1 and treatment duration. Apneas, hyperthermia, and tachycardia were associated with maximal dose. Our data did not demonstrate a difference in the incidence of NEC associated with characteristics of PGE1 treatment. Cumulative PGE1 dose is associated with gastrointestinal adverse effects in neonates. Lower doses should be considered in neonates expecting prolonged PGE1 treatment.

Prostaglandin E1 Is an Efficient Molecular Tool for Forest Leech Blood Sucking.

From a survival perspective, it is hypothesized that leech saliva exhibits certain physiological effects to ensure fast blood-feeding, including analgesia, anesthesia, and anti-inflammation to stay undetected by the host and vasodilatation and anti-hemostasis to ensure a steady, rapid, and sustained blood flow to the feeding site. Many anti-hemostatic compounds have been identified in leech saliva, such as hirudin, calin, and bdellin A. However, no specific substance with direct vasodilatory and anti-inflammatory function has been reported from forest leech saliva. Herein, using activity-guided analysis, prostaglandin E1 (PGE1) was identified for the first time as an efficient molecular tool for forest leech blood sucking. The structure of PGE1 was analyzed by nuclear magnetic resonance spectroscopy and high-resolution electrospray ionization mass spectroscopy. PGE1 was found to be primarily distributed in the leech salivary gland (1228.36 ng/g body weight). We also analyzed how forest leech PGE1 affects platelet aggregation, skin vascular permeability, bleeding time, and pain. Results indicated that PGE1 efficiently inhibited platelet aggregation induced by adenosine diphosphate (ADP) (5 &#x3bc;M) with an IC50 of 21.81 &#xb1; 2.24 nM. At doses of 10, 100 nM, and 1 &#x3bc;M, PGE1 increased vascular permeability by 1.18, 5.8, and 9.2 times. It also prolonged bleeding time in a concentration-independent manner. In the formalin-induced mouse paw pain model, PGE1 suppressed acute pain. To the best of our knowledge, this is the first report on PGE1 in invertebrates. The functions of PGE1, such as vasodilation, platelet aggregation inhibition, anti-inflammation, and pain alleviation, may facilitate the ingestion of host blood by leeches.