Quantitative Evaluation of Release and Reuptake of Adrenergic Transmitter in the Rabbit Heart

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Abstract
Drugs known to block the reuptake of noradrenaline into sympathetic nerves were compared with respect to their potency to increase the outflow of noradrenaline from the isolated rabbit heart in response to nerve stimulation. At a dose level where the drugs tested strongly and equally blocked the uptake of exogenous noradrenaline, they appeared to form two distinct groups differing in potentiation of the noradrenaline outflow. Thus, at optimal concentrations cocaine and desipramine were about equally efficient and increased the outflow of nor adrenaline by about 100%, while protriptyline, phenoxybenzamine and LU 3–010 raised the outflow by about 200 %. The effect of cocaine and desipramine on nerve stimulation‐induced outflow of noradrenaline was further increased by addition of the a‐blocking drug Hydergin. It is concluded that while all the drugs used increase the outflow of noradrenaline in response to nerve stirnulation by strongly depressing reuptake of the transmitter into the neurons, PBA, protriptyline and LU 3–010 apparently in addition augment the amount of noradrenaline re leased from the nerves, possibly by counteracting some braking mechanism normally restricting the release of noradrenaline in response to nerve stimulation.

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