Pharmacological characterization of the bradykinin B2 receptor antagonist MEN16132 in rat in vitro bioassays

The pharmacological profile of the bradykinin B2 receptor antagonist MEN16132 at the rat B2 receptor has been investigated and compared with that of icatibant (formerly Hoe 140). Antagonist affinity has been measured through radioligand binding experiments with membranes prepared from uterine and airway tissue. MEN16132 inhibited [3H]bradykinin binding with subnanomolar affinity (pKi values 10.4 and 10.1 in the uterus and airways, respectively), and was about 3-fold less potent than icatibant (pKi values 10.9 and 10.5).Antagonist potency has been estimated towards bradykinin-induced contractility of uterine and urinary bladder smooth muscle preparations. In these assays MEN16132 (pKB: 9.7 both in uterus and bladder) was about 10-fold more potent than icatibant [pKB: 8.8 in uterus, and pKB 8.0 in urinary bladder, as from Meini, S., Patacchini, R., Giuliani, S., Lazzeri, M., Turini, D., Maggi, C.A., Lecci, A., 2000a. Characterization of bradykinin B2 receptor antagonists in human and rat urinary bladder. Eur. J. Pharmacol. 388, 177–182]. Washout experiments conducted in the uterine preparation indicated for MEN16132 (100 nM) a slower reversibility than icatibant (300 nM).Altogether present results indicate that MEN16132 displays high affinity and potency also for the rat bradykinin B2 receptor, and thus is suitable for further investigations in pathophysiological models in this species.