Benextramine, a covalently binding alpha-
adrenoceptor blocking agent, potentiated the action of
noradrenaline but not
isoprenaline in guinea pig isolated right atria. This potentiation was probably caused by inhibition of neuronal uptake. When the
benextramine was washed from the tissues for 60 min, no potentiation of the action of
noradrenaline was observed. This easily reversed inhibition of neuronal uptake by
benextramine contrasts with the effects of
desipramine and
phenoxybenzamine because the potentiating effect of these drugs was unaffected by 60 min of washing. The presence of
benextramine also caused a small
tachycardia in both rabbit and guinea pig right atria which was probably due to the release of endogenous
noradrenaline.
Clonidine a presynaptic alpha 2-adrenoceptor agonist, inhibited the responses to electrical field stimulation. Pretreatment with
benextramine greatly diminished the effect of
clonidine. This alpha 2-adrenoceptor antagonism was not reversed by washing the
benextramine from the tissue for 240 min. We conclude that
benextramine is a readily reversible inhibitor of neuronal uptake and an irreversible antagonist of presynaptic alpha 2-adrenoceptors.