Antagonism of Reserpine by Intraventricular Bretylium

Abstract

BRETYLIUM, as shown by Boura and Green¹, causes an inhibition of sympathetic nervous transmission by a blocking action at adrenergic post-ganglionic neurons. Reserpine also inhibits peripheral sympathetic nervous transmission but does so by depleting adrenergic nerve endings of the transmitter substance norepinephrine². It also causes a depression of central nervous activity (tranquillization or sedation) which is associated with depletion of brain stores of norepinephrine³ and 5-hydroxytryptamine⁴. It seemed of interest to see if bretylium could block the actions of reserpine on the central nervous system. In order to study interactions of the two drugs on the central nervous system both had to be given so that effective concentrations of each could be attained at this site. Investigations by Boura et al.⁵ in which labelled bretylium, which is a quaternary amine, was administered to cats, demonstrated that only small quantities reached the central nervous system. In order to attain a higher concentration the bretylium in the present work was administered intraventricularly.