PRESYNAPTIC EFFECT OF BETA-ADRENOCEPTOR ANTAGONISTS ON NORADRENERGIC NEURONS

Besides their blocking effect on .beta.-adrenoceptors, propranolol and some related drugs also reduced the effect of sympathetic nerve stimulation by inhibiting noradrenaline (norepinephrine, NA) release. The mechanism of this presynaptic effect is unclear. The present data on the subject and the evidence in favor of the suggested mechanisms were discussed. Some .beta.-adrenoceptor antagonists could mask the presynaptic inhibitory effect, particularly in vivo (cat nictitating membrane and dog hindlimb). The possible relevance of a presynaptic action to the antiarrhythmic effects and other therapeutic actions of these drugs were discussed. In vitro studies were performed with rabbit and guinea-pig vas deferens and atria. The ideal .beta.-adrenoceptor antagonist to use to demonstrate an inhibitory effect on NA release in vivo is apparently one which lacks membrane stabilizing properties and therefore would also be unlikely to inhibit reuptake of the release NA into sympathetic neurons. The compound should have a relatively weak depressant effect on cardiac output so that it does not cause reflex stimulation of the sympathoadrenal system and peripheral vasoconstriction.