Various steroids (1 7‐fl‐oestradiol, cortico‐sterone, deoxycorticosterone, progesterone, testosterone and androsterone) produced a dose‐dependent inhibition of the uptake of 3H‐noradrenaline by the Uptake2 mechanism in the isolated perfused heart. It is suggested that these results may explain the potentiating effects of such steroids on the responses of vascular smooth muscle to catecholamines.

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The neuromuscular blocking effects of the new monoquaternary analogue of pancuronium, Org NC 45, have been investigated in anaesthetized patients. In different doses administered as a single i.v. bolus or as an initial bolus followed by several small maintenance doses or by a continuous infusion. Org NC 45 appears to be approximately as potent as pancuronium, but has a more rapid onset of action, considerably shorter duration of action and faster recovery rate than pancuronium. It showed no cumulative effects even after 10 maintenance doses were injected in succession. Doses of 0.08 mg kg-1 provided ideal intubating conditions in 90--95 s. Infusions of Org NC 45 provided much smoother control of neuromuscular blockade than did pancuronium. No cardiovascular side-effects were noted even at the greatest dose (0.12 mg kg-1) used. Org NC 45 has clear advantages over pancuronium and represents a potentially valuable addition to the armamentarium of clinically useful muscle relaxants.

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Summary1. Twenty-one haloalkylamine derivatives were tested as inhibitors of both the neuronal uptake of 3H-noradrenaline (NA) by the Uptake, mechanism and the extraneuronal uptake of 3H-NA by the Uptake2 mechanism in the isolated rat heart.2. At a concentration of 50 ,M most of the compounds tested caused a significant inhibition of both uptake processes, although there were wide differences in the relative effects on Uptake1 and Uptake2. Some tentative structure activity relationships for uptake inhibition were formulated from these results. were significantly more potent than phenoxybenzamine as Uptake2 inhibitors, and were all less potent than phenoxybenzamine as Uptake, inhibitors. The compound SKF 550 is the most potent and selective inhibitor of Uptake2 so far described. It has an IC50 for Uptake2 of 0-08 /.M, and an IC50 for Uptake1 of approximately 40 0 zuM. 5. Comparison of the present results with the known activities of these blocking agents suggests that no correlation exists between adrenoceptor blocking activity and ability of the substances to act as inhibitors of Uptake2 or Uptake1. IntroductionCatecholamines are accumulated by two different uptake mechanisms in the rat heart. There is an uptake of catecholamine into adrenergic nerve terminals