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

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.