The use of ex vivo platelet aggregation to confirm the in vivo α 2-adrenoreceptor antagonist effect of idazoxan in man

The aggregation of human platelets induced by adrenaline has been used as a test system to investigate the in vivo effect of the α 2-adrenoreceptor antagonist idazoxan during initial intravenous studies with increasing doses. The inhibitory effect of idazoxan in vitro was confirmed; addition of idazoxan to platelet suspensions prior to adrenaline caused a competitive inhibition of the aggregatory response by specific antagonism of the platelet α 2-adrenoreceptor. Following intravenous infusions of increasing doses of idazoxan to volunteers, a dose-dependent inhibition of the ex vivo aggregatory response to adrenaline was observed in isolated platelet suspensions compared to predose values. The inhibitory effects of idazoxan in vivo declined in a biphasic manner with a more rapid fall over the first hour. This reflects the kinetics of the drug in plasma and the semilogarithmic nature of the concentration-response line observed in vitro. Intravenous doses of 100 and 300 μg kg were demonstrated to be effective antagonist doses of the platelet α 2-adrenoreceptor in healthy volunteers.