Abstract |
1. The effects of a novel, potent and orally active nonpeptide bradykinin B2 receptor antagonist, FR167344 (N-[N-[3-[(3-bromo-2-methylimidazo[1,2-a]pyridin-8-yl)oxymethyl]-2 ,4-dichlorophenyl]-N-methylaminocarbonylmethyl]-4-(dimethylamin ocarbonyl) cinnamylamide hydrochloride) were tested in three different in vivo models of inflammation. 2. Oral administration of FR167344 inhibited carrageenin-induced paw oedema in rats ( carrageenin: 1%, 0.1 ml per animal, intraplantar), with an ID50 of 2.7 mg kg(-1) at 2 h after carrageenin injection (n=10 or 11). 3. Oral administration of the compound also inhibited kaolin-induced writhing ( kaolin: 250 mg kg(-1), i.p.) in mice, with ID50 of 2.8 mg kg(-1) in 10 min writhing and 4.2 mg kg(-1) in 15 min writhing (n=19 or 20). 4. Additionally, oral administration of FR167344 inhibited caerulein-induced pancreatic oedema with an ID50 of 13.8 mg kg(-1) as well as increases in amylase and lipase of blood samples with ID50 of 10.3 and 7.4 mg kg(-1), respectively, in rats (n=10). 5. These results show that FR167344 is an orally active, anti-inflammatory and anti-nociceptive agent in carrageenin-induced paw oedema, kaolin-induced writhing and caerulein-induced pancreatitis. FR167344 may have therapeutic potential against inflammatory diseases by oral administration and it may be a useful tool for studying the involvement of B2 receptors in various in vivo models of inflammation.
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Authors | M Asano, C Hatori, N Inamura, H Sawai, J Hirosumi, T Fujiwara, K Nakahara |
Journal | British journal of pharmacology
(Br J Pharmacol)
Vol. 122
Issue 7
Pg. 1436-40
(Dec 1997)
ISSN: 0007-1188 [Print] England |
PMID | 9421292
(Publication Type: Journal Article)
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Chemical References |
- Antidiarrheals
- Bradykinin Receptor Antagonists
- Excipients
- FR 167344
- Gastrointestinal Agents
- Pyridines
- Receptor, Bradykinin B2
- Receptors, Bradykinin
- Kaolin
- Ceruletide
- Carrageenan
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Topics |
- Administration, Oral
- Animals
- Antidiarrheals
- Bradykinin Receptor Antagonists
- Carrageenan
- Ceruletide
- Disease Models, Animal
- Excipients
- Gastrointestinal Agents
- Inflammation
(chemically induced, drug therapy)
- Kaolin
- Male
- Mice
- Mice, Inbred ICR
- Pain
(chemically induced, drug therapy)
- Pancreatitis
(chemically induced)
- Pyridines
(administration & dosage, pharmacology)
- Rats
- Rats, Sprague-Dawley
- Receptor, Bradykinin B2
- Receptors, Bradykinin
(drug effects)
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