Hoe 140 a new potent and long acting bradykinin‐antagonist: <i>in vivo</i> studies

Wirth, Klaus; Hock, Franz J.; Albus, Udo; Linz, Wolfgang; Alpermann, H. G.; Anagnostopoulos, H.; Henke, St.; Breipohl, Gerhard; König, Wilfried Α.; Knolle, Jochen; Schölkens, Bernward A.

doi:10.1111/j.1476-5381.1991.tb12249.x

Cited by 644 publications

(299 citation statements)

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“…Normal Wistar rats were intravenously treated with HOE 140 (100 or 300 ìg kg¢), a bradykinin Bµ receptor antagonist (Wirth et al 1991), 5 min before the administration of glucose. In these rats, the peak rise in blood glucose was significantly increased in comparison with the blood glucose levels measured in saline-treated rats (Fig.…”

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confidence: 99%

Insulin Sensitivity, Clearance and Release in Kininogen‐Deficient Rats

Damas

Bourdon

Lefèbvre

1999

Experimental Physiology

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summaryInsulin sensitivity of kininogen-deficient rats was compared with that of normal rats using euglycaemic hyperinsulinaemic glucose clamping. Anaesthetized animals were infused with 2-50 mU kg¢ min¢ of insulin and the glucose infusion rates needed to maintain euglycaemia were determined. Maximum glucose uptake, insulin sensitivity index and insulin clearance were reduced in kininogen-deficient rats. Captopril increased the amount of glucose needed to maintain euglycaemia during infusion of 2 and 10 mU kg¢ min¢ of insulin in normal rats, but had no effect in kininogen-deficient rats. Anaesthetized rats of both strains were given an intraperitoneal injection of glucose and the evolution of blood glucose was followed for 120 min. The peak increase was higher in kininogen-deficient rats. Similar larger increases in blood glucose were observed after glucose injection in normal rats previously treated with HOE 140, a bradykinin Bµ receptor antagonist. After glucose injection, plasma insulin increased in both groups of rats but reached lower levels in kininogen-deficient animals. These results suggest that bradykinin is involved not only in the clearance of glucose and insulin by the tissues during insulin infusion but also that bradykinin can affect the release of insulin after a glucose load.

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confidence: 99%

Insulin Sensitivity, Clearance and Release in Kininogen‐Deficient Rats

Damas

Bourdon

Lefèbvre

1999

Experimental Physiology

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“…Recently,`second-generation' B 2 receptor antagonists including Hoe 140 (D-Arg-[Hyp 3 , Thi 5 , DTic 7 , Oic 8 ]bradykinin) and S 16118 , Thi 5 , D-Tic 7 , Oic 8 ]bradykinin) have been obtained. They are highly potent and long-acting against bradykinin-induced responses and can be used to inhibit in¯ammation in vivo (Hock et al, 1991;Wirth et al, 1991b;Cheronis et al, 1992;FeÂ leÂ tou et al, 1995b). Hoe 140 and S 16118 showed inhibitory e ects on various animal models, such as carrageenininduced paw oedema, caerulein-induced pancreatitis and bronchial microvascular leakage (Wirth et al, 1991b;Griesbacher & Lembeck, 1992;Bertrand et al, 1993;FeÂ leÂ tou et al, 1995a).…”

Section: Introductionmentioning

confidence: 99%

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

Asano¹,

Hatori²,

Inamura³

et al. 1997

British J Pharmacology

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1 The e ects of a novel, potent and orally active nonpeptide bradykinin B 2 receptor antagonist, FR167344 (N -[N -[3 -[(3 -bromo-2 -methylimidazo[1,2-a]pyridin-8-yl)oxymethyl]-2,4-dichlorophenyl]-Nmethylaminocarbonylmethyl]-4-(dimethylaminocarbonyl) cinnamylamide hydrochloride) were tested in three di erent in vivo models of in¯ammation. 2 Oral administration of FR167344 inhibited carrageenin-induced paw oedema in rats (carrageenin: 1%, 0.1 ml per animal, intraplantar), with an ID 50 of 2.7 mg kg 71 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 71 , i.p.) in mice, with ID 50 of 2.8 mg kg 71 in 10 min writhing and 4.2 mg kg 71 in 15 min writhing (n=19 or 20). 4 Additionally, oral administration of FR167344 inhibited caerulein-induced pancreatic oedema with an ID 50 of 13.8 mg kg 71 as well as increases in amylase and lipase of blood samples with ID 50 of 10.3 and 7.4 mg kg 71 , respectively, in rats (n=10). 5 These results show that FR167344 is an orally active, anti-in¯ammatory and anti-nociceptive agent in carrageenin-induced paw oedema, kaolin-induced writhing and caerulein-induced pancreatitis. FR167344 may have therapeutic potential against in¯ammatory diseases by oral administration and it may be a useful tool for studying the involvement of B 2 receptors in various in vivo models of in¯ammation.

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“…Icatibant has been shown to be inactive against a great variety of mediators including angiotensin II, noradrenaline, histamine, acetylcholine, 5-hydroxytryptamine, substance P and neurokinin A (Lembeck et al, 1991;Wirth et al, 1991;Damas & Remacle-Volon, 1992;Rhaleb et al, 1992). Since icatibant does not inhibit the action of des-Arg9-BK at the B1 receptor Rhaleb et al, 1992), the present results point towards an involvement of B2, but not B. receptors in collagenase-induced paw oedema.…”

Section: Discussionmentioning

confidence: 54%

“…For reasons of clarity only the first 30 min after the collagenase injection are given in the graph; thereafter, until the end of the observation period, the difference in the sensitivity scores for rats pretreated with icatibant and for control rats remained unchanged (*P <0.02 mammalian collagenases in their mode of action (Hatheway, 1990). Clostridial collagenases act on all known types of collagen and can cleave native triple helical collagen into small fragments, mostly tripeptides, whereas mammalian collagenases are specific for certain types of collagen and often cleave only one protein bond in a polypeptide chain of triple helical collagen, resulting in two polypeptide fragments (Han et al, 1992 (Lembeck et al, 1991) or Hoe-140 Wirth et al, 1991)], caused a pronounced reduction of the collagenaseinduced paw oedema and of plasma protein extravasation. In addition, icatibant abolished the increase in sensitivity scores in a behaviour test after subplantar injection of collagenase in unanaesthetized rats.…”

Section: Discussionmentioning

confidence: 99%

Mediation by bradykinin of rat paw oedema induced by collagenase from Clostridium histolyticum

Legat

Griesbacher

Lembeck

1994

British J Pharmacology

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1 Collagenases are thought to play a major role in the pathology of gas gangrene caused by Clostridium histolyticum, because they can destroy the connective tissue barriers. We investigated possible mediators involved in the oedema formation and plasma protein extravasation which follow the injection of a collagenase (EC 3.4.24.3) from Clostridium histolyticum into one hind paw of anaesthetized rats. 2 The magnitude of the oedema following a subplantar injection was dependent on the dose of collagenase (30, 100 and 300 Lg) injected. It reached its maximum within 30 min and remained unchanged for at least 5 h. Plasma protein extravasation into the paw was most pronounced within 20min of the injection. Heat-inactivated collagenase was ineffective. named Hoe-140) reduced oedema formation in a dose-dependent manner with a maximal reduction of around 65% at a dose of 100 nmol kg-' (s.c.). A significant effect could already be observed at a dose of 10 nmol kg-. The duration of the effect of icatibant (100 nmol kg-1) was found to be at least 3 h. These results demonstrate the high potency and long duration of action of icatibant. Pretreatment of rats with the bradykinin B, antagonist, des-Arg9-[Leu8]-BK did not affect collagenase-induced paw oedema. Thus, the observed collagenase-induced effects are mainly mediated by BK through activation of B2 receptors. 4 Pretreatment of adult rats with capsaicin (125 mg kg-', s.c.) three weeks before the collagenase injection caused a significant attenuation of the paw oedema and of plasma extravasation but was significantly less effective than icatibant (100 nmol kg-', s.c.). The non-peptide substance P antagonist, CP-96,345 (10 ltmol kg', i.v.) significantly reduced collagenase-induced oedema formation to a degree comparable with that seen after capsaicin pretreatment. The inhibition by the substance P antagonist was significantly smaller than that seen after icatibant. The inhibitory effect of icatibant in capsaicinpretreated rats, or of icatibant together with CP-96,345 in untreated rats, was not greater than that of significantly reduced the bradykinin-induced paw oedema. These findings indicate that collagenase leads to the release of bradykinin; bradykinin then stimulates afferent C-fibre terminals and causes the release of substance P and probably also neurokinin A, which augment the oedema-inducing effect of bradykinin. 5 Indomethacin or mepyramine plus cimetidine failed to inhibit collagenase-induced paw oedema. Thus, prostaglandins and histamine do not seem to be involved in collagenase-induced paw oedema. 6 After subplantar injection of collagenase, the sensitivity scores in a modified formalin-test rapidly increased during the first 10 min. This increase was abolished by pretreatment with icatibant (100 nmol kg '-, s.c.) indicating that the stimulation of nociceptive afferent neurones following injection of collagenase is due to the action of released kinins.7 In conclusion, bradykinin appears to be the main mediator of inflammation induced by a collagenase from Clost...

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Hoe 140 a new potent and long acting bradykinin‐antagonist: in vivo studies

Cited by 644 publications

References 33 publications

Insulin Sensitivity, Clearance and Release in Kininogen‐Deficient Rats

Insulin Sensitivity, Clearance and Release in Kininogen‐Deficient Rats

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

Mediation by bradykinin of rat paw oedema induced by collagenase from Clostridium histolyticum

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Hoe 140 a new potent and long acting bradykinin‐antagonist: in vivo studies

Cited by 644 publications

References 33 publications

Insulin Sensitivity, Clearance and Release in Kininogen‐Deficient Rats

Insulin Sensitivity, Clearance and Release in Kininogen‐Deficient Rats

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

Mediation by bradykinin of rat paw oedema induced by collagenase from Clostridium histolyticum

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