Effect of T : 0632, a Cholecystokinin_A Receptor Antagonist, on Experimental Acute Pancreatitis

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Author(s)

Abstract

Effects of a new cholecystokinin (CCK)<SUB>A</SUB>-receptor antagonist, T-0632 [sodium (<I>S</I>)-I-(2-flu orophenyl)-2, 3-dihydro-3-[(3-isoquinolinylcarbonyl)amino]-6-methoxy-2-oxo-1<I>H</I>-indole-3-propanoate], on caerulein-induced and pancreatic duct ligation-induced pancreatitis models were studied and compared with the CCK<SUB>A</SUB>-receptor antagonist loxiglumide and the orally active protease inhibitor camostate, respectively. In rats, orally administered T-0632 potently prevented the caerulein-induced increases in pancreatic digestive enzymes in plasma and suppressed the histological changes in the pancreas. The estimated ED<SUB>50</SUB> values of T-0632 and loxiglumide were 0.0092 and 8.9 mg/kg, respectively. In dogs, T-0632 (0.1, 1 mg/kg, i.d.)prevented the caerulein-induced increase in plasma amylase activity in a dose-dependent manner. Loxiglumide (100 mg/kg, i.d.)did not show any preventive effects. In pancreatic duct ligation (6 hr)induced pancreatitis of the rat, T-0632 (0.001-0.1 mg/kg, p.o.)partially prevented both the increase in plasma amylase activity and the histological changes in the pancreas, whereas camostate (10, 100 mg/kg, p.o.)did not show any preventive effects. In pancreatic duct ligation (3 hr)-induced pancreatitis, caerulein injection (1 μg/kg, s.c.)caused a further increase in plasma amylase activity, and T-0632 (0.01, 0.1 mg/kg, p.o.)dose-dependently decreased the aggravation by caerulein. We conclude that T-0632 showed preventive effects on all of these pancreatitis models by oral or intraduodenal administration. These results suggest that CCK plays an important role in progression and aggravation of acute pancreatitis, and T-0632 may have a therapeutic value in these disease states.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 73(2), 105-112, 1997-02-01

    The Japanese Pharmacological Society

References:  31

Codes

  • NII Article ID (NAID)
    10008677028
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    00215198
  • NDL Article ID
    4153685
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  NDL  J-STAGE 
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