A contribution, from a possible local anaesthetic action, to the effects of yohimbine on evoked noradrenaline overflow.

Both yohimbine (0.1 to 10 microM) and phentolamine (10 microM) increased the tritium overflow evoked by electrical stimulation (2.5 Hz, 1 ms, 15 V, for 90 s every 20 min) of mouse isolated vas deferens previously incubated with (-)-[3H]noradrenaline. At their maximally effective concentrations, phentolamine (10 microM) produced an effect that was sustained over the 2 h of the experiment while the effect of yohimbine (6 microM) decreased by about 60% over the first 40 min and was then sustained at a lower level. At higher concentrations of yohimbine, the increase in evoked tritium overflow was less marked and at the highest concentration tested (30 microM) evoked overflow was reduced below the levels seen before exposure to the drug. It is concluded that at concentrations maximally effective in inhibiting the presynaptic alpha-adrenoceptor-mediated mechanism controlling transmitter release, the known local anaesthetic effect of yohimbine may contribute to the overall effect on evoked transmitter overflow.