PRESYNAPTIC AND POSTSYNAPTIC EFFECTS OF YOHIMBINE STEREOISOMERS ON NORADRENERGIC TRANSMISSION IN THE PULMONARY-ARTERY OF THE RABBIT

Effects on noradrenergic neurotransmission of five stereoisomers of yohimbine and of the closely related compound yohimbol were studied in strips of the pulmonary artery of the rabbit. In some experiments the tissue was preincubated with 3H-noradrenaline. Three effects were observed. Firstly, antagonism to the contractile effect of noradrenaline and of sympathetic nerve stimulation; the antagonism reflected competitive blockade of postsynaptic α-adrenoceptors. Secondly, an increase in the stimulation-evoked overflow of total tritium and 3H-noradrenaline; the increase appeared to be due to blockade of presynaptic α-adrenoceptors. Thirdly, an increase in the basal outflow of 3H-3,4-dihydrophenylglycol, presumably by impairment of the vesicular storage of 3H-noradrenaline. According to their relative potencies in eliciting these effects, the drugs could be divided into three groups. Rauwolscine, β-yohimbine and yohimbol preferentially blocked the presynaptic α-adrenoceptor; rauwolscine and β-yohimbine, like yohimbine, at low concentrations increased the contractile response to sympathetic nerve stimulation. Corynanthine preferentially blocked the postsynaptic α-adrenoceptor. Pseudoyohimbine and 3-epi-α-yohimbine were very weak antagonists at either receptor; they mainly accelerated the basal outflow of 3H-3,4-dihydroxyphenylglycol. From these results and those of a previous study it is concluded that, in a series of twelve α-adrenolytic drugs, rauwolscine shows the greatest preference for presynaptic and corynanthine the greatest preference for postsynaptic α-adrenoceptors. In view of the chemical similarity of the two compounds these opposite properties are striking. Corynanthine and rauwolscine might be useful tools for the subclassification of α-adrenoceptors. © 1979 Springer-Verlag.