Recombinant PD-1/TIM3 bispecific antibody(L&L vision biopharmaceuticals)

Aims The aim of this study was to examine the effects of bisoprolol (BIS), a selective β1‐adrenoceptor antagonist without partial agonistic activity, on noradrenaline‐ and phenylephrine‐evoked venoconstriction in man using the dorsal hand vein compliance technique.Methods Twelve healthy male volunteers participated in three weekly experimental sessions. Subjects were allocated to treatments and sessions on a double‐blind basis. In each session either BIS 5 mg (BIS5), or BIS 10 mg (BIS10), or placebo was administered orally, and noradrenaline acid tartrate (0.1–33.33 ng min−1 ) followed by phenylephrine hydrochloride (0.033–10 μg min−1 ) was infused into the dorsal hand vein. Systolic and diastolic blood pressure and heart rate were also measured.Results Both noradrenaline and phenylephrine produced dose‐dependent venoconstriction: the geometric mean ED50 for noradrenaline was 3.21 ng min−1 and for phenylephrine 135.04 ng min−1; the potency ratio (noradrenaline/phenylephrine) was 42. Both BIS5 and BIS10 significantly decreased the venoconstriction to noradrenaline (ANOVA; P<0.005), and to phenylephrine (ANOVA; P<0.001). The antagonism of the venoconstrictor responses was also reflected in a significant increase in logED50 values for both noradrenaline (ANOVA; P<0.005), and phenylephrine (ANOVA; P<0.0025) in the presence of both doses of BIS. Both doses of BIS significantly decreased heart rate (ANOVA; P<0.0001), and systolic blood pressure (ANOVA; P<0.0025).Conclusions Bisoprolol can antagonize α1‐adrenoceptor mediated venoconstriction in the human dorsal hand vein in vivo through a mechanism which remains to be elucidated.