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

• Published in: European journal of pharmacology Vol. 130; no. 3; p. 219
• Main Authors: Magyar, K, Fekete, M I, Tekes, K, Török, T L
• Format: Journal Article
• Language: English
• Published: Netherlands 04-11-1986
• Subjects: Animals; Antidepressive Agents - pharmacology; Calcium - pharmacology; Cocaine - pharmacology; Female; Male; Muscle Contraction - drug effects; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Norepinephrine - metabolism; Piperazines - pharmacology; Pulmonary Artery - metabolism; Rabbits; Receptors, Adrenergic, alpha - drug effects; Sodium - metabolism; Yohimbine - pharmacology
• ISSN: 0014-2999
• DOI: 10.1016/0014-2999(86)90271-2

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.