The action of trelibet, a new antidepressive agent on [ 3H]noradrenaline release from rabbit pulmonary artery

Abstract

Trelibet, a new antidepressant, used at 10 −7–10 −4 M failed to affect the [ 3H]noradrenaline ([ 3H]NA) release evoked from the isolated main pulmonary artery of the rabbit low frequency (2 Hz) nerve stimulation whether the neuronal uptake inhibitor cocaine (3 × 10 −5 M) was present or not. Its metabolite (EGYT-2760) however, potentiated the nerve-evoked release of [ 3H]NA. In the absence of cocaine both the resting and the stimulation-evoked release of 3H increased in response to EGYT-2760. These effect were accompanied by muscle contraction. The EGYT-2760-potentiated transmitter release was inhibited either by exogenously applied 1-noradrenaline (10 −6 M) or clonidine (10 −6 M), preferential agonists of presynaptic α 2-adrenoceptors. The 1-noradrenaline-induced inhibition of transmitter release potentiated by EGYT-2760 was antagonized by 3 × 10 −7 M yohimbine, a preferential α 2-adrenoceptor inhibitor. In the absence of cocaine, Ca 2+ removal from the external medium failed to affect the 3H outflow-increasing effect of EGYT-2760 but abolished the nerve-evoked release-potentiating action of this compound. It is concluded that the metabolite of trelibet exerts a ‘yohimbine-like’ action, as well as a ‘tyramine-like’ effect in peripheral sympathetic nerve fibres.