ozagrel / Generic mfg. - LARVOL DELTA

TP receptor antagonism superior to biosynthesis inhibition for blockade of the prostanoid component in IgE triggered human small airway constriction (ERS 2026) - "Histamine H1 (mepyramine)+CysLT1 (montelukast) receptor antagonism reduced response (Emax 52±6%) The remaining contraction was abolished by COX1 inhibition (FR122047), TXAS inhibition (ozagrel), or TP receptor antagonism (SQ-29548). Selective inhibition of the biosynthesis of the individual prostanoids was associated with shunting and switching between the prostanoids. Clinically, TP receptor antagonism would be preferred to effectively blunt the prostanoid component of the mast cell-driven bronchoconstriction."

Respiratory Diseases

Shared Genetic Risk Between Acute Pancreatitis and Metabolic Syndrome Converges on a BCAT1-Positive Fibroblast Subpopulation and MAPK14-Driven Inflammation. (PubMed, FASEB J) - "Ozagrel was prioritized as an exploratory candidate with favorable predicted binding affinities and requires further validation...MAPK14-associated inflammation and Bcat1-positive fibroblast remodeling may contribute to AP aggravation under metabolic disturbance. These findings provide candidate biomarkers for SAP prediction and support BCAT1 and MAPK14 as potential mechanistic targets."

Journal • Dyslipidemia • Inflammation • Metabolic Disorders • Pancreatitis • BCAT1 • IL1R1 • MAPK14

Endovascular treatment for subarachnoid hemorrhage during pregnancy followed by minimum approaches for cerebral vasospasm. (PubMed, Surg Neurol Int) - "We performed EVT, followed by minimum required prevention and treatment of cerebral vasospasm using fasudil hydrochloride, aspirin, and ozagrel sodium, as these agents seem to be associated with fewer adverse effects at 26 weeks of gestation. We reported the case of a pregnant patient with SAH who underwent EVT, followed by the minimum required prevention and treatment for cerebral vasospasm. Clinicians should carefully select the medical approaches, including pharmacotherapies for both pregnant women with SAH and the fetus, considering radiation exposure and medication risks."

Journal • Cardiovascular • Hematological Disorders • Obstetrics • Pain • Subarachnoid Hemorrhage

Targeting the Vim-PGI2 Pathway Enhances CD8+ T Cell-Mediated Antitumor Immunity in Breast Cancer. (PubMed, Hum Mutat) - "Both exogenous PGI2 supplementation and ozagrel treatment reversed these effects. In conclusion, the Vim-PGI2 axis is identified as a key regulator of CD8+ T cell immunity in breast cancer, representing a potential therapeutic target and a critical consideration in anticoagulant management during cancer immunotherapy."

IO biomarker • Journal • Breast Cancer • Oncology • Solid Tumor • CD8 • GZMB • IFNG • KLRD1 • PTGIS

Thromboxane synthase inhibitors: a new perspective in osteogenesis imperfecta. (HMGC 2026) - "Materials and We evaluated the safety and efficacy of picotamide and ozagrel, compared to alendronate and control, in wild-type (WT), Col1a2oim/+, and Col1a2oim/oim mice. The therapeutic repurposing of TXAS inhibitors could represent a promising new approach for the treatment of patients with osteogenesis imperfecta."

Genetic Disorders

A Case of Development and Rapid Increase in the Microbleeds after Pipeline Placement for an Intracranial Unruptured Aneurysm. (PubMed, NMC Case Rep J) - "Adjustments to medications, including delaying aspirin and adding antihypertensives, were made. Sodium ozagrel was introduced but later discontinued due to further increases in cerebral microbleeds...Even when antiplatelet medications are maintained within the optimal therapeutic range, there remains a risk of cerebral hemorrhage. This risk must be carefully considered, and appropriate adjustments to antiplatelet therapy are essential during the perioperative period."

Journal • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Thrombosis • Vascular Neurology

Thromboxane A2, not prostaglandin D2, drives the prostanoid-mediated component of mast cell-induced constriction in human small airways (ERS 2025) - "The remaining contraction was abolished (p<0.05) by unselective COX inhibitor indomethacin, selective COX-1 inhibitor FR 122,047, or TP receptor antagonist SQ-29,548, whereas COX-2 inhibitor lumiracoxib had no effect (E max: 57±7%). The selective thromboxane (TX) A synthase inhibitor ozagrel prevented the prostanoid component of the contraction (p<0.05), whereas the prostaglandin (PG) D synthase inhibitor PPCA unexpectedly increased it (E max: 67±7%, p<0.05)...TXA 2 rather than PGD 2 mediates the contractile prostanoid component. The findings may explain why PGD 2 antagonism failed in treatment of asthma."

Asthma • Immunology • Respiratory Diseases

Symptomatic Cerebral Vasospasm After Clipping of an Unruptured Intracranial Aneurysm: A Case Report and Literature Review. (PubMed, Cureus) - "Treatment with intra-arterial fasudil injection and continuous intravenous fasudil with ozagrel sodium resulted in complete neurological recovery. Cerebral vasospasm after UIA clipping is uncommon and may be overlooked, thereby resulting in serious sequelae."

Journal • Cardiovascular • Vascular Neurology

Medical Management of a Meningioma Presenting as an Ischemic Stroke: A Case Report and Review of the Literature. (PubMed, Cureus) - "Instead, intensive medical therapy was initiated, consisting of triple antiplatelet therapy (aspirin, clopidogrel, and ozagrel) and osmotic therapy with intravenous glycerol. This case highlights the potential for aggressive medical management to obviate emergent neurosurgery in select patients. Further study is warranted to identify candidates most likely to benefit from such an approach."

Journal • Brain Cancer • Cardiovascular • Hematological Disorders • Ischemic stroke • Meningioma • Oncology • Solid Tumor

Analysis of hemorrhagic transformation and intracerebral hemorrhage under combination therapy with alteplase and antiplatelets or anticoagulants, using the Japanese Adverse Drug Event Report database. (PubMed, PLoS One) - "HT and/or ICH signals were detected in patients receiving alteplase in combination with aspirin, P2Y12 inhibitors, cilostazol, ozagrel sodium, direct oral anticoagulants, warfarin potassium, heparin group, or argatroban. The findings from this study may help in understanding the risk of HT and ICH induced by rtPA in patients taking antiplatelet or anticoagulant medications, as well as in promoting the appropriate use of rtPA. Further prospective observational studies and randomized controlled trials are needed to assess these finding."

Adverse events • Journal • Cardiovascular • Cerebral Hemorrhage • Diabetes • Hematological Disorders • Hypertension • Ischemic stroke • Metabolic Disorders • Thrombosis

Comparative effectiveness of Panax notoginseng saponins-related agents and antiplatelet agents in ischemic stroke: A systematic review and network meta-analysis. (PubMed, J Ethnopharmacol) - "Overall, our study indicates that initiating PNS plus aspirin therapy within 14 days of symptom onset, is associated with favorable functional outcomes in patients with IS compared with therapy comprising clopidogrel plus aspirin, indobufen, or aspirin alone. As such, PNS plus aspirin presents a potentially viable approach for the clinical treatment of IS, thereby contributing to a reduction in patient disability."

HEOR • Journal • Retrospective data • Review • Cardiovascular • Ischemic stroke

Successful Recanalization Using the Direct Aspiration First Pass Technique for Acute Carotid Stent Thrombosis Following Carotid Artery Stenting. (PubMed, Cureus) - "Due to a partial contrast filling defect within the stent after recanalization, 80 mg of ozagrel sodium was administered intravenously and prasugrel was delivered via a nasogastric tube. Subsequent angiography showed no re-occlusion or stenosis, and the procedure was completed. No recurrence of cerebral infarction was observed postoperatively, and the patient was transferred to a rehabilitation facility."

Journal • Cardiovascular • CNS Disorders • Hematological Disorders • Thrombosis

Submucosal Esophageal Hematoma: A Rare Hemorrhagic Complication Following Neuroendovascular Therapy. (PubMed, J Neuroendovasc Ther) - "An 80-year-old woman on clopidogrel and aspirin underwent Pipeline flow diversion with adjunctive coil embolization for an unruptured right internal carotid-posterior communicating artery aneurysm under general anesthesia without complications...After CT confirmed hemostasis, antiplatelet therapy was resumed with intravenous ozagrel sodium on postoperative day 3, switching to oral prasugrel on day 7...The patient was discharged on day 24 without symptoms or complications. In addition to previously reported cases, the presented case suggests that conservative management with temporary antiplatelet interruption and early resumption after hemostasis can lead to favorable outcomes in SEH cases associated with neuroendovascular therapy requiring antiplatelet therapy."

Journal • Anesthesia • Cardiovascular • Hematological Disorders • Pain • Vascular Neurology

Early Antithrombotic Therapy in Acute Ischemic Stroke. (PubMed, J Neuroendovasc Ther) - "Other antiplatelet drugs, such as clopidogrel, cilostazol, prasugrel, and intravenous ozagrel sodium, are also available within the Japanese Health Care Insurance System...Warfarin continues to be the anticoagulant of choice for secondary stroke prevention in patients with mechanical valve replacements. In patients who have undergone intravenous thrombolysis, antithrombotic therapy is generally delayed for up to 24 hours, although there are no definitive guidelines for the period during and immediately after mechanical thrombectomy. This review provides an overview of the current status of antithrombotic therapy for acute ischemic stroke."

Journal • Review • Atrial Fibrillation • Cardiovascular • Hematological Disorders • Ischemic stroke

Impact of Clazosentan on Vasospasm Reduction and Functional Recovery after Aneurysmal Subarachnoid Hemorrhage. (PubMed, Neurol Med Chir (Tokyo)) - "In every hospital in Japan, until 2022, the primary treatment for preventing delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) involved a combination of ozagrel sodium (Oz), fasudil hydrochloride (Fs), cilostazol, and statins. No significant difference was observed in the primary endpoint of functional outcome at discharge; however, a significant improvement in functional outcome was observed in the clazosentan group at 6 months (96.3% vs. 70.4%, p<0.05). Clazosentan significantly reduced the incidence of CV and improved functional outcomes in patients with aSAH compared to Oz+Fs."

Journal • Cardiovascular • Hematological Disorders • Subarachnoid Hemorrhage

Preventing Fluid Retention After Subarachnoid Haemorrhage During Administration of Endothelin Receptor Antagonist. (PubMed, Adv Exp Med Biol) - "Prevention of delayed cerebral infarction (DCI) due to cerebral vasospasm after subarachnoid haemorrhage (SAH) has been done with intravenous Rho kinase inhibitors (ROCKI), ozagrel sodium (TXA2I), selective ROCKI infusion (ROCKI i.a.), and cerebrospinal fluid (CSF) drainage. The endothelin receptor antagonist (ERA, clazosentan) became available in 2022 and is said to be highly recommended for DCI prevention, while fluid retention such as pleural effusion and pulmonary oedema accumulation is often experienced...We examined the results of blood sampling on admission, echocardiography, chest computed tomography (CT), with postoperative DCI, and hydrocephalus requiring cerebrospinal fluid shunt (hydro), and symptomatic fluid retention requiring albumin and furosemide (third fluid space)...Our experience suggests that age may be the most influential factor. Based on these results, we have also found that by avoiding the use of ERA in patients older than 80 years,..."

Journal • Cardiomyopathy • Cardiovascular • CNS Disorders • Congestive Heart Failure • Heart Failure • Respiratory Diseases • Subarachnoid Hemorrhage • Ventriculomegaly • NPPB

Postoperative Management of Aneurysmal Subarachnoid Hemorrhage (PubMed, No Shinkei Geka) - "In Japan, fasudil hydrochloride and ozagrel sodium are widely used to prevent vasospasms; however, their effects are sometimes insufficient. This was demonstrated in a recent randomized phase 3 trial, leading to the approval of clazosentan by the Pharmaceuticals and Medical Devices Agency in Japan. Recent advances in our understanding of subarachnoid hemorrhage will facilitate improved management to reduce the incidence of DCI."

Journal • Review • Cardiovascular • Hematological Disorders • Subarachnoid Hemorrhage

Deciphering the role of thromboxane A2 in mast cell-induced bronchoconstriction within human small airways (ERS 2024) - "Combined pretreatment with the antagonists for H1 receptors (mepyramine; 1 µM) and CysLT1 receptors (montelukast; 1 µM) reduced the anti-IgE induced contraction by 52±6%. The residual component of the contraction was abolished by addition of the cyclooxygenase (COX)-1 enzyme inhibitor FR 122,047 (1 µM), thromboxane(TX) A synthase inhibitor ozagrel (10 µM) or the TXA2 TP receptor antagonist SQ-29,548 (1 µM)...Discussion Mast cell dependent contractions of human bronchi are mediated by histamine, cysteinyl-leukotrienes and COX-1 generated contractile prostanoids acting on the TP receptor. In addition, the inhibitor data support that TXA2 is the primary contractile prostanoid in human small airways and that inhibition of its formation redirects formation towards PGD2, suggesting a shunt of the endoperoxide PGH2."

Asthma • Immunology • Respiratory Diseases

Fasudil hydrochloride and ozagrel sodium combination therapy for patients with aneurysmal subarachnoid hemorrhage: a cross-sectional study using a nationwide inpatient database. (PubMed, J Pharm Health Care Sci) - "Fasudil hydrochloride and ozagrel sodium had different mechanisms of action, suggesting a synergistic effect of combination therapy. However, a comparison of fasudil hydrochloride monotherapy and combination therapy of fasudil hydrochloride and ozagrel sodium showed no difference in the prognostic effect. Therefore, it was suggested that fasudil hydrochloride monotherapy may be sufficient."

Combination therapy • Journal • Observational data • Cardiovascular • Hematological Disorders • Subarachnoid Hemorrhage

Pharmacokinetic/Pharmacodynamic assessment of the structural refinement of clopidogrel focusing on the balance between bioactivation and deactivation. (PubMed, Drug Metab Dispos) - "Clopidogrel and prasugrel, both members of the thienopyridine class of antiplatelet drugs, are well established for their variability in individual responsiveness and for a high number of bleeding events, respectively. Under similar exposure to active metabolites, these compounds have demonstrated enhanced antiplatelet activity and a diminished risk of bleeding compared to clopidogrel. The D3-clopidogrel-ozagrel conjugate was found to exert a synergistic therapeutic effect."

Journal • PK/PD data

Design, synthesis, and evaluation of the novel ozagrel-paeonol codrug with antiplatelet aggregation activities as a potent anti-stroke therapeutic agent. (PubMed, Front Pharmacol) - "Other than aspirin, no standard, accepted, or effective treatment for acute ischemic stroke has been established. Molecular docking analysis further demonstrated that the compound interacts with residues located in the active binding sites of the target proteins. The codrugs synthesized in this study display promising pharmacological activities and have the potential for development as an oral formulation."

Journal • Cardiovascular • Ischemic stroke

Initial real-world experience of clazosentan for subarachnoid hemorrhage in Japan. (PubMed, World Neurosurg ) - "Clinical outcomes of the new protocol were comparable to those of conventional protocol. Clazosentan may simplify anti-vasospasm treatment. Fluid retention was a specific side-effect of clazosentan, which requires attention especially in the first half of the CVS period."

Journal • Real-world • Real-world evidence • Hematological Disorders • Subarachnoid Hemorrhage

Defining the prostanoid component in mast cell-dependent constriction of isolated human small airways (ERS 2023) - "Combined pre-treatment with the antagonists for H1 receptors (mepyramine; 1 µM) and CysLT1 receptors (montelukast; 1 µM) reduced the anti-IgE induced contraction by 52±6%, n=11. The residual component of the contraction was abolished by addition of the cyclooxygenase (COX)-1 enzyme inhibitor FR 122,047 (1 µM, n=6), but not by the COX-2 inhibitor etoricoxib (1 µM, n=10). The prostanoid-dependent contractile component was alternatively eliminated by either the thromboxane A synthase inhibitor ozagrel (10 µM, n=5) or the thromboxane TP receptor antagonist SQ-29,548 (1 µM, n=6). DiscussionMast cell dependent contractions of human bronchi are mediated by histamine, cysteinyl-leukotrienes and COX-1 generated contractile prostanoids acting on the TP receptor. In addition, the inhibitor data support that thromboxane A2 is the primary contractile prostanoid in human small airways.; Endoscopy and interventional pulmonology; Imaging; Cell and..."

Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

Defining the Prostanoid Component in Mast Cell-dependent Constriction of Isolated Human Small Airways (ATS 2023) - "This residual component of the contractions to both mast cell activators in the presence of mepyramine and montelukast was abolished by addition of the cyclooxygenase (COX)-1 enzyme inhibitor FR 122,047 (1 µM, n=5-6), but not by the COX-2 inhibitor etoricoxib (1 µM, n=5-10). The prostanoid-dependent contractile component of the anti-IgE response was abolished by addition of either the thromboxane A synthase (TXAS) inhibitor ozagrel (10 µM, n=5) or the thromboxane TP receptor antagonist SQ-29,548 (1 µM, n=6)... The mast cell dependent contractions of human bronchi are mediated by histamine, cysteinyl-leukotrienes and COX-1 generated contractile prostanoids acting on the TP receptor. The relative contribution of the TP receptor was greater during hyperosmolarity than after anti-IgE challenge. In addition, the inhibitor data support that thromboxane A2 is the primary contractile prostanoid during IgE induced mast cell activation, whereas for..."

Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

Endothelium dysfunction in hind limb arteries of male Zucker Diabetic-Sprague Dawley rats. (PubMed, Biochem Pharmacol) - "In this study we aimed to test endothelial dysfunction, the vasodilator effects of a proteinase-activated receptor 2 (PAR2) agonist (2fLIGRLO), and thromboxane A synthase inhibitor (ozagrel) on PAR2 vasodilation in hind limb arteries ex vivo, using Zucker Diabetic-Sprague Dawley (ZDSD) rats, a model of type 2 diabetes...We used acetylcholine, 2fLIGRLO, and nitroprusside with wire-myograph methods to compare relaxations of femoral, and saphenous arteries from diabetic ZDSD (21-23 wks) to age-matched normoglycemic SD...Hind limb arteries of ZDSD exhibit endothelium dysfunction having less GPCR agonist induced vasodilation by endothelial NO-release. Different expression of several endothelial genes in ZDSD vs SD aortas, including PAR2, suggests altered inflammatory, and angiogenesis signaling pathways in the endothelium of ZDSD."

Journal • Preclinical • Cardiovascular • Diabetes • Hypertension • Metabolic Disorders • Peripheral Arterial Disease • Type 2 Diabetes Mellitus • PGF