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  • Title: Effects of the serine protease inhibitor gabexate mesilate on purified pancreatic phospholipase A2.
    Author: Hesse B, Lankisch PG, Kunze H.
    Journal: Pharmacol Res Commun; 1984 Jul; 16(7):637-45. PubMed ID: 6433363.
    Abstract:
    The catalytic activity of purified porcine pancreatic phospholipase A2 is competitively inhibited by the cationic amphiphilic serine protease inhibitor gabexate mesilate (ethyl 4-(6-guanidinohexanoyloxy) benzoate methanesulfonate). A Ki of 1.3 X 10(-4)M was found when 1,2-dioctanoyl-sn-glycero-3-phosphorylcholine was used as a substrate. The main metabolites of this drug, 6-guanidinocaproic acid and ethyl p-hydroxy-benzoate, had no effect in concentrations up to 10(-2)M. From the high gabexate mesilate concentrations required to reduce phospholipase A2 activity and from the considerably lower drug concentrations sufficient to cause beneficial effects in acute pancreatitis it is concluded that direct inhibition of pancreatic phospholipase A2 cannot be the cause of the therapeutic results, improvement of the symptoms and prognosis of acute pancreatitis.
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