Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1991 Mar;102(3):774–777. doi: 10.1111/j.1476-5381.1991.tb12249.x

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

K Wirth, FJ Hock, U Albus, W Linz, HG Alpermann, H Anagnostopoulos, St Henke, G Breipohl, W König, J Knolle, BA Schölkens
PMCID: PMC1917928  PMID: 1364852

Abstract

1 The potency, duration of action and tolerability of Hoe 140, a novel and highly potent bradykinin (BK) antagonist in vitro, has been tested in different in vivo models and compared with the well-known BK antagonist D-Arg-[Hyp2, Thi5,8, D-Phe7]BK.

2 Hoe 140 is highly potent and long acting in inhibiting BK-induced hypotensive responses in the rat. Four hours after s.c. administration of 20nmol kg-1, inhibition still amounted to 60% whereas the effect of 200nmol kg-1 of D-Arg-[Hyp2, Thi5,8, D-Phe7]BK was not significant.

3 BK-induced bronchoconstriction in guinea-pigs was strongly inhibited by Hoe 140. The magnitude and duration of inhibition confirmed the findings obtained in the blood pressure experiments in the rat.

4 Carrageenin-induced inflammatory oedema of the rat paw was considerably inhibited at i.v. doses between 0.1 and 1 mgkg-1.

5 In conscious dogs, intravenous doses of 0.01 and 0.1 mgkg-1 of Hoe 140 and D-Arg-[Hyp2, Thi5,8, D-Phe7]BK were well tolerated. At doses of 1 mgkg-1 adverse effects occurred that were attributed to the residual BK agonistic activity of both compounds.

6 Hoe 140 has been shown to be a highly potent and long acting BK antagonist in vivo in different animal species and models. This makes it appropriate to investigate further the physiological and pathophysiological role of BK.

Full text

PDF
774

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barnes P. J., Chung K. F., Page C. P. Inflammatory mediators and asthma. Pharmacol Rev. 1988 Mar;40(1):49–84. [PubMed] [Google Scholar]
  2. Chapman R. W., Danko G., Siegel M. I. Effect of propranolol on pulmonary function and bronchoconstrictor responsiveness in guinea pigs and rats. Pharmacol Res Commun. 1985 Feb;17(2):149–163. doi: 10.1016/0031-6989(85)90061-x. [DOI] [PubMed] [Google Scholar]
  3. Christiansen S. C., Proud D., Cochrane C. G. Detection of tissue kallikrein in the bronchoalveolar lavage fluid of asthmatic subjects. J Clin Invest. 1987 Jan;79(1):188–197. doi: 10.1172/JCI112782. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Costello A. H., Hargreaves K. M. Suppression of carrageenan-induced hyperalgesia, hyperthermia and edema by a bradykinin antagonist. Eur J Pharmacol. 1989 Nov 21;171(2-3):259–263. doi: 10.1016/0014-2999(89)90118-0. [DOI] [PubMed] [Google Scholar]
  5. FELDBERG W., LEWIS G. P. THE ACTION OF PEPTIDES ON THE ADRENAL MEDULLA. RELEASE OF ADRENALINE BY BRADYKININ AND ANGIOTENSIN. J Physiol. 1964 May;171:98–108. doi: 10.1113/jphysiol.1964.sp007364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fuller R. W., Dixon C. M., Cuss F. M., Barnes P. J. Bradykinin-induced bronchoconstriction in humans. Mode of action. Am Rev Respir Dis. 1987 Jan;135(1):176–180. doi: 10.1164/arrd.1987.135.1.176. [DOI] [PubMed] [Google Scholar]
  7. Griesbacher T., Lembeck F., Saria A. Effects of the bradykinin antagonist B4310 on smooth muscles and blood pressure in the rat, and its enzymatic degradation. Br J Pharmacol. 1989 Mar;96(3):531–538. doi: 10.1111/j.1476-5381.1989.tb11850.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hargreaves K. M., Troullos E. S., Dionne R. A., Schmidt E. A., Schafer S. C., Joris J. L. Bradykinin is increased during acute and chronic inflammation: therapeutic implications. Clin Pharmacol Ther. 1988 Dec;44(6):613–621. doi: 10.1038/clpt.1988.202. [DOI] [PubMed] [Google Scholar]
  9. Hock F. J., Wirth K., Albus U., Linz W., Gerhards H. J., Wiemer G., Henke S., Breipohl G., König W., Knolle J. Hoe 140 a new potent and long acting bradykinin-antagonist: in vitro studies. Br J Pharmacol. 1991 Mar;102(3):769–773. doi: 10.1111/j.1476-5381.1991.tb12248.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kaufman M. P., Coleridge H. M., Coleridge J. C., Baker D. G. Bradykinin stimulates afferent vagal C-fibers in intrapulmonary airways of dogs. J Appl Physiol Respir Environ Exerc Physiol. 1980 Mar;48(3):511–517. doi: 10.1152/jappl.1980.48.3.511. [DOI] [PubMed] [Google Scholar]
  11. Lau W. A., Rechtman M. P., Boura A. L., King R. G. Synergistic potentiation by captopril and propranolol of bradykinin-induced bronchoconstriction in the guinea-pig. Clin Exp Pharmacol Physiol. 1989 Nov;16(11):849–857. doi: 10.1111/j.1440-1681.1989.tb01524.x. [DOI] [PubMed] [Google Scholar]
  12. Proud D., Kaplan A. P. Kinin formation: mechanisms and role in inflammatory disorders. Annu Rev Immunol. 1988;6:49–83. doi: 10.1146/annurev.iy.06.040188.000405. [DOI] [PubMed] [Google Scholar]
  13. Selwyn B. M., Figueroa C. D., Fink E., Swan A., Dieppe P. A., Bhoola K. D. A tissue kallikrein in the synovial fluid of patients with rheumatoid arthritis. Ann Rheum Dis. 1989 Feb;48(2):128–133. doi: 10.1136/ard.48.2.128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. WINTER C. A., RISLEY E. A., NUSS G. W. Carrageenin-induced edema in hind paw of the rat as an assay for antiiflammatory drugs. Proc Soc Exp Biol Med. 1962 Dec;111:544–547. doi: 10.3181/00379727-111-27849. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES