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Hoe 140 a new potent and long acting bradykinin‐antagonist: in vivo studies
Author(s) -
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.
Publication year - 1991
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1991.tb12249.x
Subject(s) - bradykinin , in vivo , antagonist , pharmacology , bradykinin receptor , medicine , chemistry , biology , receptor , microbiology and biotechnology
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‐[Hyp 2 , Thi 5,8 , d ‐Phe 7 ]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‐[Hyp 2 , Thi 5,8 , d ‐Phe 7 ]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‐[Hyp 2 , Thi 5,8 , d ‐Phe 7 ]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.