1. Preliminary studies in healthy normotensive subjects with a selective α2−adrenoceptor antagonist 2 − {2 − (1,4 − benzodioxanyl)} − 2 − imidazoline (RX781094) in a dose of 0.2 μg/kg intravenously are described.
2. There was a transient increase in blood pressure, and plasma noradrenaline, 10–20 min after dosing and an associated reduction in heart rate. These observations are consistent with blockade of peripheral presynaptic α2−adrenoceptors in man.
3. The pressor responses to α−methylnoradrenaline, which has relatively selective agonist effects on α2−adrenoceptors, were markedly attenuated between 0.5 and 3.0 h after dosing (dose ratio > 20).
4. The pressor responsiveness to intravenous phenylephrine, a selective α1−adrenoceptor agonist, was only slightly reduced (dose ratio 1.7 ±0.8), as was the blood pressure rise after intravenous noradrenaline (dose ratio 1.7 ± 0.7).
5. The differential effects on the agonist pressor responses are consistent with antagonism by RX781094 of post−junctional α2−adrenoceptors on vascular smooth muscle.
