The action of trelibet, a new antidepressive agent on [3H]noradrenaline release from rabbit pulmonary artery.
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 X 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 alpha 2-adrenoceptors. The 1-noradrenaline-induced inhibition of transmitter release potentiated by EGYT-2760 was antagonized by 3 X 10(-7) M yohimbine, a preferential alpha 2-adrenoceptor inhibitor. In the absence of cocaine, Ca2+ 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.
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D005260:Female; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000378:metabolism; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D012964:Sodium / Q000378:metabolism; D015016:Yohimbine / Q000494:pharmacology
D000928:Antidepressive Agents; D010879:Piperazines; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; C040401:EGYT 475; D012964:Sodium; D003042:Cocaine; D002118:Calcium; D009638:Norepinephrine