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Effects of loxiglumide on experimental acute pancreatitis in comparison with gabexate mesilate.
- Source :
-
Arzneimittel-Forschung [Arzneimittelforschung] 1998 Jan; Vol. 48 (1), pp. 65-9. - Publication Year :
- 1998
-
Abstract
- Loxiglumide ((+/-)-4-(3,4-dichlorobenzamido)-N-(3-methoxypropyl)-N- pentylglutaramic acid, CAS 107097-80-3, CR 1505) is a cholecystokinin-A (CCK-A) receptor antagonist. In this report, the effects of loxiglumide and gabexate mesilate were studied on three experimental acute pancreatitis models induced by caerulein, sodium taurocholate + caerulein and closed duodenal loop. The intravenous injection of loxiglumide at 3 and 10 mg/kg (6 times at hourly intervals) significantly inhibited an increase in serum amylase activity induced by the intraperitoneal injection of caerulein (50 micrograms/kg i.p., 6 times at hourly intervals) in mice. But gabexate mesilate at 10, 30 and 60 mg/kg did not. The intravenous infusion of loxiglumide at 18 and 60 mg/kg/h showed a life prolonging effect in the lethal necrotizing pancreatitis, induced by the subcutaneous injection of caerulein (50 micrograms/kg s.c., 4 times at 2 h intervals) after the injection of sodium taurocholate (10%, 0.1 ml/body) into the common bile duct, cumulative survival rates being 86 and 90%, respectively. Gabexate mesilate at 180 mg/kg/h showed the prolonging effect (cumulative survival rates 75%). The intravenous injection of loxiglumide at 6, 18 and 60 mg/kg/h significantly inhibited an increase in total ascitic lipase activity, and plasma amylase and lipase activity of rats with closed duodenal loop. These results suggest that CCK plays an important role in the progression of acute pancreatitis, and that loxiglumide may have a therapeutic potential for pancreatitis.
- Subjects :
- Acute Disease
Amylases metabolism
Animals
Ceruletide
Duodenum physiology
Female
Gabexate administration & dosage
Hormone Antagonists administration & dosage
Injections, Intravenous
Male
Mice
Mice, Inbred ICR
Organ Size drug effects
Pancreas drug effects
Pancreas enzymology
Pancreatitis chemically induced
Pancreatitis physiopathology
Proglumide administration & dosage
Proglumide therapeutic use
Rats
Rats, Sprague-Dawley
Serine Proteinase Inhibitors administration & dosage
Gabexate therapeutic use
Hormone Antagonists therapeutic use
Pancreatitis drug therapy
Proglumide analogs & derivatives
Receptors, Cholecystokinin antagonists & inhibitors
Serine Proteinase Inhibitors therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 0004-4172
- Volume :
- 48
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Arzneimittel-Forschung
- Publication Type :
- Academic Journal
- Accession number :
- 9522035