Article

Effects of a nonpeptide bradykinin B2 receptor antagonist, FR167344, on different in vivo animal models of inflammation.

Department of Pharmacology, Exploratory Research Laboratories, Fujisawa Pharmaceutical, Tsukuba, Ibaraki, Japan.
British Journal of Pharmacology (impact factor: 4.41). 01/1998; 122(7):1436-40. DOI:10.1038/sj.bjp.0701534 pp.1436-40
Source: PubMed

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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Keywords

10 min writhing
 
15 min writhing
 
amylase
 
anti-inflammatory
 
anti-nociceptive agent
 
B2 receptors
 
blood samples
 
caerulein-induced pancreatitis
 
carrageenin-induced paw oedema
 
FR167344 inhibited caerulein-induced pancreatic oedema
 
FR167344 inhibited carrageenin-induced paw oedema
 
inflammatory diseases
 
kaolin
 
kaolin-induced writhing
 
Oral administration
 
orally active
 
orally active nonpeptide bradykinin B2 receptor antagonist
 
useful tool
 
various
 
vivo models
 

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