Gabexate mesilate and camostate: New inhibitors of phospholipase A2 and their influence on the alpha-amylase activity in serum of patients with acute pancreatitis

Freise, J.; Schmidt, F. W.; Magerstedt, P.; Schmid, Kurt

doi:10.1016/s0009-9120(85)80044-8

Cited by 24 publications

(14 citation statements)

References 7 publications

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“…Purified Factor XII (70 ,g/ml), PK (1 mg/ml), and aI-antiprotease inhibitor were provided by Dr. Robin Pixley; fibronectin degradation products (FNDPs) (1.3 mg/ml) were donated by Dr. Andrei Budzynski, and Factor V was donated (0.93 mg/ml) by Dr. Angie Annamalai, all of Temple University, Philadelphia, PA. Foy, a specific inhibitor of cathepsin G (20) and a monospecific polyclonal antibody to HNE (21), were generously provided by Dr. Fred Kueppers, Temple University, Philadelphia, PA. Eglin, an inhibitor of cathepsin G and HNE, was generously provided by Dr. Hans-Peter Schnebli, CibaGeigy AG, Basel, Switzerland. HNE was purified to homogeneity by the procedure of Baugh and Travis (22).…”

Section: Methodsmentioning

confidence: 99%

Human neutrophils contain and bind high molecular weight kininogen.

Gustafson¹,

Wachtfogel²,

Kaufman³

et al. 1989

J. Clin. Invest.

101

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Section: Methodsmentioning

confidence: 99%

Human neutrophils contain and bind high molecular weight kininogen.

Gustafson¹,

Wachtfogel²,

Kaufman³

et al. 1989

J. Clin. Invest.

101

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“…ONO3307 and FOY007 are new synthetic agents, guanidino acid esters, which inhibit a number of esterases such as trypsin, phospholipase A2, kallikrein. plasmin, thrombin and C |r and C |S esterases [32][33][34][35].…”

Section: Discussionmentioning

confidence: 99%

Protection by a New Synthetic Protease Inhibitor, ONO3307, of the Rat Exocrine Pancreas during Acute Edematous Pancreatitis Induced by a Supramaximal Dose of Caerulein in Comparison with FOY007

Hirano

Manabe²,

Tobe³

1992

Pharmacology

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The present study investigated the protective effects of the new potent synthetic protease inhibitors, ONO3307 (4-sulfamoyl phenyl-4-guanidinobenzoate methanesulfonate) and FOY007 (gabexate misilate), on the exocrine pancreas in rat caerulein-induced acute pancreatitis in both in vitro and in vivo experiments. These protease inhibitors prevented hyperamylasemia, pancreatic edema, congestion of amylase, redistribution of lysosomal enzyme in acinar cells, and lactic dehy-drogenase (LDH) discharge from dispersed acini. They also inhibited the cathepsin B leakage from the lysosomes in a dose-dependent manner in doses of 2–10 mg/kg·h of ONO-3307 and 20-50 mg/kg·h of FOY007. These results indicate that both ONO3307 and FOY007 exert protective effects against pancreatitis at subcellular levels in lysosomes and cellular or organelle membranes. Proteases appear to be important in the pathogenesis and development of acute pancreatitis, and low-molecular-weight protease inhibitors may be of clinical use in the treatment of acute pancreatitis.

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“…The advantageous influence of FOY on acute pancreatitis is not only explicable by the inhibition of various proteases in serum and pancreas, thanks to its wide spectrum (wider than aprotinin) as an antiprotease [6,7]. Its stabilizing effect on cellular and lysosomal membranes [6] could decrease the output of proteolytic enzymes from the inflamed pancreas, which are well known to be involved in the severe complications of pancreatitis, such…”

Section: Discussionmentioning

confidence: 99%

“…Gabexate mesilate is a synthetic protease inhibitor with a small molecular weight (417.48). FOY has been shown to inhibit the enzymatic activity of a variety of enzymes, such as trypsin, kallikrein (kinin system), thrombin (coagulation system), C1 esterase (complement system), and phopholipase A2 [6,7], which has a main pathophysiologic role in the pancreatic autodigestion, leading to acute pancreatitis [4,6,7].…”

Section: Introductionmentioning

confidence: 99%

Effect on hemodynamics of therapeutic infusion of gabexate mesilate (FOY) in experimental acute pancreatitis

et al. 1989

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Acute pancreatitis was induced in ten anesthetized dogs by retrograde injection for bile mixed with trypsin into the pancreatic duct. Five animals were treated with i.v. infusion of gabexate mesilate in a dose of 1 mg/kg per hour. Hemodynamic data were regulary monitored during a 10-h observation period. Cardiac output (CO), mean arterial pressure (MAP), and left ventricular stroke volume (LVSV) decreased rapidly in untreated animals. An increase of systemic vascular resistance (SVR) and pulmonary vascular resistance (PVR) was observed in dogs without treatment. Gabexate mesilate given as a therapy significantly improved the hemodynamic parameters. The study demonstrates an advantageous influence of synthetic antiprotease gabexate mesilate on the course of acute experimental pancreatitis.

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Gabexate mesilate and camostate: New inhibitors of phospholipase A2 and their influence on the alpha-amylase activity in serum of patients with acute pancreatitis

Cited by 24 publications

References 7 publications

Human neutrophils contain and bind high molecular weight kininogen.

Human neutrophils contain and bind high molecular weight kininogen.

Protection by a New Synthetic Protease Inhibitor, ONO3307, of the Rat Exocrine Pancreas during Acute Edematous Pancreatitis Induced by a Supramaximal Dose of Caerulein in Comparison with FOY007

Effect on hemodynamics of therapeutic infusion of gabexate mesilate (FOY) in experimental acute pancreatitis

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