Magyar K, Fekete M I, Tekes K, Török T L
Eur J Pharmacol. 1986 Nov 4;130(3):219-27. 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.
新型抗抑郁药曲利贝特（Trelibet）在10⁻⁷ - 10⁻⁴ M浓度下，无论是否存在神经元摄取抑制剂可卡因（3×10⁻⁵ M），均未能影响兔离体主肺动脉经低频（2 Hz）神经刺激诱发的[³H]去甲肾上腺素（[³H]NA）释放。然而，其代谢产物（EGYT - 2760）增强了神经诱发的[³H]NA释放。在不存在可卡因的情况下，EGYT - 2760使³H的静息释放和刺激诱发释放均增加。这些效应伴有肌肉收缩。EGYT - 2760增强的递质释放受到外源性应用的1 - 去甲肾上腺素（10⁻⁶ M）或可乐定（10⁻⁶ M）的抑制，它们是突触前α₂ - 肾上腺素能受体的选择性激动剂。EGYT - 2760增强的1 - 去甲肾上腺素诱导的递质释放抑制作用被3×10⁻⁷ M育亨宾拮抗，育亨宾是一种选择性α₂ - 肾上腺素能受体抑制剂。在不存在可卡因的情况下，从外部介质中去除Ca²⁺未能影响EGYT - 2760增加³H流出的作用，但消除了该化合物增强神经诱发释放的作用。结论是，曲利贝特的代谢产物在外周交感神经纤维中发挥“育亨宾样”作用以及“酪胺样”效应。
