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

• Published in: British journal of pharmacology 1991-03, Vol.102 (3), p.774-777
• Main Authors: Wirth, K., Hock, F.J., Albus, U., Linz, W., Alpermann, H.G., Anagnostopoulos, H., Henke, St, Breipohl, G., König, W., Knolle, J., Schölkens, B.A.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Blood Pressure - drug effects; Bradykinin - analogs & derivatives; Bradykinin - antagonists & inhibitors; Bradykinin - pharmacology; Bronchoconstriction - drug effects; Dogs; Edema - prevention & control; Female; Guinea Pigs; Heart Rate - drug effects; Hormones. Endocrine system; Male; Medical sciences; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1991.tb12249.x

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 20 nmol kg−1, inhibition still amounted to 60% whereas the effect of 200 nmol 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 mg kg−1. 5 In conscious dogs, intravenous doses of 0.01 and 0.1 mg kg−1 of Hoe 140 and d‐Arg‐[Hyp2, Thi5,8, d‐Phe7]BK were well tolerated. At doses of 1 mg kg−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.