Linked Life Data

16183055

Source:http://linkedlifedata.com/resource/pubmed/id/16183055

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-3
pubmed:dateCreated
2005-10-11
pubmed:abstractText
The effects of R-102444 ((2R, 4R)-4-lauroyloxy-2-[2-[2-[2-(3-methoxy)phenyl]ethyl]phenoxy]ethyl-1-methylpyrrolidine hydrochloride) and its active metabolite R-96544 ((2R, 4R)-2-[2-[2-[2-(3-methoxy)phenyl]ethyl]phenoxy]ethyl-4-hydroxy-1-methylpyrrolidine hydrochloride), potent and selective 5-hydroxytryptamine 2A (5-HT2A) receptor antagonists, on development of pancreatitis were investigated in experimental models of acute and chronic pancreatitis. Rat acute pancreatitis was induced by caerulein (20 microg/kg) intraperitoneal injection and by pancreatic duct ligation. In both the models, serum amylase and lipase activities were markedly increased. R-102444 dose-dependently reduced these enzyme activities at a dose range of 10 to 100 mg/kg (p.o.) for the caerulein model and 0.3 to 10 mg/kg (p.o.) for the ligation model. In a mouse model of acute pancreatitis induced by a choline-deficient, ethionine (0.5%)-supplemented diet, subcutaneous administration of R-96544 (10-100 mg/kg, bid) reduced serum amylase activity. Histological analysis showed that R-96544 dose-dependently attenuated pancreatic necrosis, inflammation and vacuolization. The effect of R-102444 was further examined in male Wistar Bonn/Kobori rats (4-9 months of age) which spontaneously show pancreatic fibrosis and parenchymal destruction compatible with human chronic pancreatitis. In Wistar Bonn/Kobori rats (from 3 to 9 months of age) fed a diet containing 0.017% and 0.17% of R-102444, pancreatic weight, pancreatic protein and amylase content were higher compared to those in non-treated pancreatitis control rats. Histological analysis showed that R-102444 suppressed parenchymal destruction and replacement with adipose tissue, indicating inhibition of pancreatic atrophy. These results clearly indicate that R-102444 and R-96544 inhibit the progression of acute and chronic pancreatitis and support the contention of possible involvement of 5-HT2A receptors in the progression of experimental pancreatitis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0014-2999
pubmed:author
pubmed:issnType
Print
pubmed:day
3
pubmed:volume
521
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
156-63
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:16183055-Acute Disease, pubmed-meshheading:16183055-Amylases, pubmed-meshheading:16183055-Animals, pubmed-meshheading:16183055-Caerulein, pubmed-meshheading:16183055-Choline, pubmed-meshheading:16183055-Chronic Disease, pubmed-meshheading:16183055-Dietary Supplements, pubmed-meshheading:16183055-Ethionine, pubmed-meshheading:16183055-Injections, Intraperitoneal, pubmed-meshheading:16183055-Ligation, pubmed-meshheading:16183055-Lipase, pubmed-meshheading:16183055-Male, pubmed-meshheading:16183055-Organ Size, pubmed-meshheading:16183055-Pancreas, pubmed-meshheading:16183055-Pancreatic Ducts, pubmed-meshheading:16183055-Pancreatitis, pubmed-meshheading:16183055-Pyrrolidines, pubmed-meshheading:16183055-Rats, pubmed-meshheading:16183055-Rats, Inbred Strains, pubmed-meshheading:16183055-Rats, Sprague-Dawley, pubmed-meshheading:16183055-Rats, Wistar, pubmed-meshheading:16183055-Receptor, Serotonin, 5-HT2A, pubmed-meshheading:16183055-Serotonin 5-HT2 Receptor Antagonists, pubmed-meshheading:16183055-Serotonin Antagonists, pubmed-meshheading:16183055-Time Factors
pubmed:year
2005
pubmed:articleTitle
Effects of R-102444 and its active metabolite R-96544, selective 5-HT2A receptor antagonists, on experimental acute and chronic pancreatitis: Additional evidence for possible involvement of 5-HT2A receptors in the development of experimental pancreatitis.
pubmed:affiliation
Pharmacology and Molecular Biology Research Laboratories, Sankyo Co., Ltd., 1-2-58 Hiromachi, Tokyo 140-8710, Japan. togawa@sankyo.co.jp
pubmed:publicationType
Journal Article, Comparative Study