Sapodifil SR (sarpogrelate sustained release) / Alvogen Korea - LARVOL DELTA

Novel serotonin 5-HT receptor antagonists derived from 4-phenylcyclohexane-5-spiro-and 5-methyl-5-phenyl-hydantoin, for use as potential antiplatelet agents. (PubMed, Pharmacol Rep) - "Our study confirmed that the 5-HT antagonists effectively suppress platelet aggregation and remain an interesting option for the development of novel antiplatelet agents with an alternative mechanism of action."

Journal • Acute Coronary Syndrome • Cardiovascular

Effect of Sarpogrelate On the Nephropathy in Type 2 Diabetes (SONATA Study) (clinicaltrials.gov) - P4; N=151; Completed; Sponsor: Yuhan Corporation; Active, not recruiting ➔ Completed

Trial completion • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus • 5-Hydroxyindoleacetic Acid

Role of serotonin in regulation of pancreatic and mesenteric arterial function in diabetic mice. (PubMed, Eur J Pharmacol) - "The vascular tension of the pancreatic, mesenteric and brain basilar arteries in diabetic and control mice were measured by myograph in the applications of angiotensin II, 5-HT, 5-HT receptor agonist 2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI), 5-HT receptor agonist sumatriptan, 5-HT receptor agonist BW723C86, 5-HT receptor antagonist Palonosetron and 5-HT receptor antagonist Sarpogrelate. The effect of 5-HT on arteries pretreated with L-NAME and sodium nitroprusside (SNP) on arteries pretreated with norepinephrine were measured...We conclude that the effect of 5-HT on the tension of pancreatic and mesenteric arteries decrease in diabetic mice. It may due to the decreased activity of 5-HT receptors and the activation of eNOS, which causes nitric oxide to release more and makes the tension of vessels decreased."

Journal • Preclinical • Diabetes • Metabolic Disorders • NOS3

Negative correlation of urinary miR-199a-3p level with ameliorating effects of sarpogrelate and cilostazol in hypertensive diabetic nephropathy. (PubMed, Biochem Pharmacol) - "Nephropathy progression in streptozotocin (STZ)-treated spontaneously hypertensive rats (SHRs), including albuminuria, collagen deposition, and histopathological changes, was alleviated by sarpogrelate and antihypertensive agent telmisartan. Collectively, these results indicate that urinary miR-199a-3p might be utilized as a marker for nephropathy treatment. We also provide evidence of the benefits of antiplatelet sarpogrelate and cilostazol in nephropathy progression."

Journal • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Hypertension • Metabolic Disorders • Nephrology • Renal Disease • MIR199A1 • TGFB1

[VIRTUAL] Severity of Transfusion-Related Acute Lung Injury in mice expressing human FcgRIIA is determined by platelet-released serotonin (GTH 2021) - "Long-term treatment with the selective serotonin reuptake inhibitor fluoxetine, to deplete the serotonin content of platelet granules, selectively abolished the aggravation of lung edema in CD32A+ mice. This effect could also be achieved by blockade of the 5-hydroxytryptamine 2A serotonin receptor with sarpogrelate when the drug was administered before or after the induction of TRALI. Conclusion Our findings identify platelet FcgRIIA/CD32A as a critical determinant of the severity of TRALI and provide a rationale for designing prophylactic and therapeutic strategies targeting the serotonin pathway to attenuate antibody-mediated TRALI in patients."

Acute Lung Injury • Immunology • Respiratory Diseases • FCGR2A

[VIRTUAL] Sarpogrelate, a Selective Serotonin2aReceptor Antagonist, Suppresses Pressure Overlaod-induced Cardiac Hypertrophy and Systolic Dysfunction Through Inhibiting Erk1/2/gata4 Pathway (AHA 2020) - "These results indicate that sarpogrelate significantly suppresses cardiomyocyte hypertrophy and the development of heart failure via at least, in part, by inhibition of ERK1/2/GATA4 pathway. These findings suggest that sarpogrelate may be an effective agent for heart failure therapy."

Cardiovascular • Congestive Heart Failure • Heart Failure • Myocardial Infarction

Sarpogrelate and rosuvastatin synergistically ameliorate aortic damage induced by hyperlipidemia in apolipoprotein E-deficient mice. (PubMed, Exp Ther Med) - "Taken together, these results suggest that the positive effects of sarpogrelate combined with rosuvastatin treatment on aortic injury may be associated with the regulation of the LOX-1/p-ERK signaling pathway. Sarpogrelate and rosuvastatin synergistically decreased aortic damage in ApoE HFD mice, and thus provide a basis for the treatment of aortic injury caused by hyperlipidemia with sarpogrelate."

Journal • Preclinical • Atherosclerosis • Cardiovascular • Dyslipidemia • Hematological Disorders • Thrombosis • APOE • IL6 • TNFA

Combinational Use of Antiplatelet Medication Sarpogrelate with Therapeutic Drug Rosuvastatin in Treating High-Cholesterol Diet-Induced Chronic Kidney Disease in ApoE-Deficient Mice. (PubMed, Biomed Res Int) - "The analysis of expression profiles at both the RNA and protein levels, using real-time quantitative polymerase chain reaction and Western blot analysis, indicated that LDL-R/CD68/LOX-1-positive monocyte/macrophage-mediated enhanced proinflammatory activation, including the significant upregulation of tumor necrosis factor-α and interleukin-6, was actually attenuated by sarpogrelate and/or rosuvastatin treatment. The findings indicated that sarpogrelate and/or rosuvastatin treatment potentially ameliorates CKD progression in patients with the aforementioned comorbid metabolic disorders."

Journal • Preclinical • Chronic Kidney Disease • Dyslipidemia • Metabolic Disorders • Nephrology • Renal Disease • APOE • CD68 • IL6 • TNFA

Effects of M-1, a major metabolite of sarpogrelate, on 5-HT-induced constriction of isolated human internal thoracic artery. (PubMed, Biol Pharm Bull) - "These results suggest that M-1 has antagonistic effects not only on the 5-HT receptor but also on the 5-HT receptor in human ITA smooth muscle cells. M-1 may be useful as a lead compound for the development of drugs for the treatment of 5-HT-induced vasospasms in CABG."

Journal • Atherosclerosis • Cardiovascular

Bioequivalence of Sarpogrelate in Healthy Chinese Subjects Under Fasting and Fed Conditions: A 4-Way Replicate Crossover Investigation by a Reference-Scaled Average Bioequivalence Approach. (PubMed, Clin Pharmacol Drug Dev) - "The 90% CIs for the ratios of lnC , lnAUC , and lnAUC were 0.8531-1.1100, 0.9616-1.0737, and 0.9550-1.0684, respectively, under fasting conditions and 0.8918-1.1076, 0.9818-1.0694, and 0.9818-1.0686, respectively, under fed conditions, which were within the RSABE acceptance limits. Food intake decreased the systemic exposure and the C of sarpogrelate by 0.9-fold and 0.5-fold, respectively."

Clinical • Journal

[VIRTUAL] Platelets Expressing FcγRIIA/CD32A Determine the Severity of Immunological Transfusion-Related Acute Lung Injury in Mice (ISTH 2020) - "Long term treatment with the selective serotonin reuptake inhibitor fluoxetine, to deplete the serotonin content of platelet granules, selectively abolished the aggravation of lung edema in CD32A+ mice. Our findings identify platelet CD32A as a critical determinant of the severity of antibody-mediated TRALI and provide a rationale for the design of serotonin pathway targeting strategies to attenuate immunological TRALI in patients."

Preclinical • Acute Lung Injury • Immunology • FCGR2A

A Study to Evaluate the Effect of Sarpogrelate on Blood Hyperviscosity (clinicaltrials.gov) - P4; N=60; Completed; Sponsor: Yuhan Corporation; Active, not recruiting ➔ Completed

Clinical • Trial completion • Cardiovascular • Peripheral Arterial Disease • Reperfusion Injury

Serotonin Signals through a Gut-Liver Axis to Regulate Hepatic Steatosis (AASLD 2018) - "Gut-derived serotonin is a direct regulator of hepatic lipid metabolism via a gut TPH1-liver HTR2A endocrine axis. And shows promise as a novel drug target to ameliorate NAFLD with minimal systemic metabolic effects."

Biosimilar • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • Obesity • Transplantation

PREDICTORS OF INTRACEREBRAL HEMORRHAGE AMONG LACUNAR STROKE PATIENTS TREATED WITH ASPIRIN: PORCELAIN STUDY SUB-ANALYSIS (ESOC 2018) - "So that we further analyzed the risk factor of “intracerebral” hemorrhage (ICeH) only among lacunar stroke patients.MethodPORCELAIN study includes three randomized, double-blinded, prospective, aspirin-comparator study conducted in Japan, i.e. S-ACESS study (2008; aspirin vs sarpogrelate), CSPS 2 study (2010; aspirin vs cilostazol) and JASAP study (2011; aspirin vs Aggrenox). During 715 days mean observation period, 129 ICeHs were documented. The history of diabetes was the only significant negative predictor of ICeH (HR=0.36; 014-0.94: p=0.037) after multivariate logistic regression analysis, whereas the history of hypertension and the blood pressure (both systolic and diastolic) on registration were not significant.ConclusionThe history of hypertension was not a significant predictor of ICeH among lacunar stroke patients treated with low-dose aspirin."

Clinical • Hypertension

Effects of sarpogrelate combined with aspirin in patients undergoing carotid endarterectomy in China: a single-center retrospective study. (PubMed) - Ann Vasc Surg - "In the present study in CEA patients, anti-platelet treatment with CA resulted in a significant risk of developing neck hematoma, increased operative blood loss and operative time compared with SA treatment. Long-term prospective studies with larger study populations are needed to further confirm the utility of SA treatment for CEA patients."

Journal • Retrospective data • Acute Coronary Syndrome • Biosimilar • Reperfusion Injury

Sarpogrelate Drug Interaction (clinicaltrials.gov) - P1; N=9; Recruiting; Sponsor: Ajou University School of Medicine; Not yet recruiting -> Recruiting

Enrollment open • Acute Coronary Syndrome • Biosimilar • Chronic Kidney Disease • Immunology

Antiplatelet Therapy of Cilostazol or Sarpogrelate with Aspirin and Clopidogrel after Percutaneous Coronary Intervention: A Retrospective Cohort Study Using the Korean National Health Insurance Claim Database. (PubMed) - PLoS One - "Sarpogrelate-containing triple antiplatelet therapy demonstrated comparable rates of MACCE prevention to the conventional dual antiplatelet therapy after PCI without significantly increasing bleeding risk during the two-year follow-up period."

Journal • Acute Coronary Syndrome • Biosimilar • Heart Failure • Reperfusion Injury

The Prevention of Contrast Induced Nephropathy by Sarpogrelate: a Prospective Randomized Controlled Clinical Trial. (PubMed, J Korean Med Sci) - P4; "This study failed to demonstrate that sarpogrelate has a renoprotective effect against contrast induced acute kidney injury."

Clinical • Journal

Effect of sarpogrelate and high-dose statin on the reduction of coronary spasm in vasospastic angina: A two by two factorial, pilot randomized study. (PubMed, Clin Cardiol) - "Sarpogrelate or high-dose statin did not significantly improve the angiographic remission rate in patients with VSA. Distal TIMI flow on initial provocation test could predict the complete remission of coronary spasm at follow-up."

Clinical • Journal

New predictors of aneurysm sac behavior after endovascular aortic aneurysm repair. (PubMed, Eur Radiol) - "• After endovascular aortic aneurysm repair (EVAR), patients with sac regression were younger and more likely to take sarpogrelate hydrochloride postoperatively than those with sac non-regression. • The incidence of postimplantation syndrome (PIS) was significantly higher in patients with sac regression. • In our analysis, PIS and thrombus density within the sac were newly identified predictors of aneurysm sac behavior after EVAR."

Journal

Effect of antiplatelet agent number, types, and pre-endoscopic management on post-polypectomy bleeding: validation of endoscopy guidelines. (PubMed, Surg Endosc) - "Analysis of this large polypectomy dataset showed that the use of low-dose aspirin, thienopyridine, or cilostazol and a combination of these is associated with increased PPB risk. Although PPB risk was high with DAPT or TAPT, PPB rate in any antiplatelet monotherapy even with a continuing strategy was low at < 5%."

Journal

Determination of epoxide impurity in sarpogrelate hydrochloride intermediate by UHPLC and column-switching liquid chromatography. (PubMed, J Pharm Biomed Anal) - "The limits of detection (LODs) of the UHPLC and column-switching liquid chromatography methods were 0.09 ppm (0.09 μg/g) and 0.33 ppm (0.33 μg/g), and the recovery rates of both methods were 87.2%-132.1% and 97.4%-100.1%, respectively. Both methods established and provided guidance for analysts to develop procedures for impurity control, especially for structures of impurity with similar matrices."

Journal

Mechanism of contractile dysfunction induced by serotonin in coronary artery in spontaneously hypertensive rats. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "A 5-HT receptor blocker, sarpogrelate, completely eliminated coronary artery contraction induced by 5-HT...At the same time, it was found that 5-HTR, IPR, and Cav1.2 protein expression and PKCδ activity were decreased, and STIM1 and Orai1 were increased in VSMCs from coronary arteries of SHRs compared with Wistar rats. These results implicate calcium-handling dysfunction mediated by the 5-HT receptor and downstream signaling pathway might lead to a reduction in 5-HT-induced contraction in SHR coronary arteries."

Journal • Preclinical • CAV1

Blockade of 5-HT receptors with sarpogrelate uncovers 5-HT receptors inhibiting the tachycardic sympathetic drive in pithed rats. (PubMed, Clin Exp Pharmacol Physiol) - "This inhibition was completely reversed by SB 258719 (a selective 5-HT receptor antagonist; 1 mg/kg, i.v.) or glibenclamide (an ATP-sensitive K channel blocker; 20 mg/kg, i.v.). These results suggest that chronic 5-HT receptor blockade uncovers a cardiac sympatho-inhibitory mechanism mediated by 5-HT receptors, involving a hyperpolarization due to the opening of ATP-sensitive K channels. Thus, these findings support the role of 5-HT receptors in the modulation of the cardiac sympathetic neurotransmission."

Journal • Preclinical

Evaluation of Isolated Vascular Response to 5HT1A, 5HT1B1D & 5HT2A Receptors Agonist & Antagonist in Chronic Endotoxemic Rats. (PubMed, Drug Res (Stuttg)) - "In first, DOI2 hydrochloride used as an agonist and sarpogrelate hydrochloride as an antagonist of 5HT2A receptor...In third, Zolmitriptan used as an agonist and GR127935 hydrochloride as an antagonist of 5HT1B1D receptor...PCR studies revealed enhanced 5HT1A receptor and diminished 5HT1B1D and 5HT2A receptor genes expression, while histopathological studies showed inflamed, damaged endothelium in endotoxemic aorta. Our data supports enhanced vasodilation and impaired vasoconstriction during endotoxemia."

Journal • Preclinical