In vitro studies on 6-fluoronoradrenaline at several peripheral sympathetic neuroeffector junctions.

Abstract

A comparison of the effects of noradrenaline and 6-fluoronoradrenaline has been made at several peripheral sympathetic neuroeffector junctions. In the rat vas deferens preparation in the presence of 1 microM cocaine, 6-fluoronoradrenaline was found to be about 9 times more potent than noradrenaline as an agonist at presynaptic inhibitory alpha 2- adrenoceptors. In the rabbit aorta, 6-fluoronoradrenaline had approximately one tenth of the potency of noradrenaline in stimulating the postsynaptic alpha 1-adrenoceptors. Furthermore 6-fluoronoradrenaline, in contrast to previous reports, appears to be a substrate for the neuronal uptake process since exposure to cocaine potentiated the inhibition of the twitch response of the vas deferens by 6-fluoronoradrenaline. In addition, 6-fluoronoradrenaline increased the spontaneous outflow of radioactivity from rabbit pulmonary artery strips prelabelled with 3H-noradrenaline and this increase was blocked by cocaine (30 microM). These results demonstrate that 6-fluoronoradrenaline is a preferential alpha 2-adrenoceptor agonist which is a substrate for the neuronal uptake process in peripheral sympathetically innervated smooth muscle preparations.