Béïque J C, Lavoie N, de Montigny C, Debonnel G
Neurobiological Psychiatry Unit, McGill University, Montréal, Canada.
Eur J Pharmacol. 1998 May 15;349(1):129-32. doi: 10.1016/s0014-2999(98)00241-6.
In vitro radioligand binding studies were carried out in rat brain membranes to assess the affinity of various reuptake inhibitors for the serotonin (5-hydroxytryptamine, 5-HT) and the norepinephrine transporters using the selective ligands [3H]cyanoimipramine and [3H]nisoxetine, respectively. The selective 5-HT reuptake inhibitors paroxetine, indalpine and fluvoxamine displayed a high affinity for the 5-HT transporter, whereas the norepinephrine reuptake inhibitor desipramine had a high affinity for the norepinephrine transporter. Duloxetine, a dual 5-HT and norepinephrine reuptake inhibitor, displayed a high affinity for both the 5-HT and the norepinephrine transporters. Interestingly, venlafaxine, a dual 5-HT and norepinephrine reuptake inhibitor, displayed only a moderate affinity for the 5-HT transporter (Ki = 74 nM) and a very low affinity for the norepinephrine transporter (Ki = 1.26 microM). The relatively low affinities of venlafaxine contrast with its potent in vivo 5-HT and norepinephrine reuptake blocking properties. These results raise the possibility that the in vivo effects on the 5-HT and norepinephrine reuptake observed with venlafaxine may not be mediated solely by its binding to the [3H]cyanoimipramine and [3H]nisoxetine binding sites.
在大鼠脑膜中进行了体外放射性配体结合研究，分别使用选择性配体[3H]氰米帕明和[3H]去甲替林来评估各种再摄取抑制剂对5-羟色胺（5-羟色胺，5-HT）和去甲肾上腺素转运体的亲和力。选择性5-HT再摄取抑制剂帕罗西汀、茚达品和氟伏沙明对5-HT转运体表现出高亲和力，而去甲肾上腺素再摄取抑制剂地昔帕明对去甲肾上腺素转运体具有高亲和力。度洛西汀，一种5-HT和去甲肾上腺素双重再摄取抑制剂，对5-HT和去甲肾上腺素转运体均表现出高亲和力。有趣的是，文拉法辛，一种5-HT和去甲肾上腺素双重再摄取抑制剂，对5-HT转运体仅表现出中等亲和力（Ki = 74 nM），对去甲肾上腺素转运体表现出非常低的亲和力（Ki = 1.26 microM）。文拉法辛相对较低的亲和力与其在体内有效的5-HT和去甲肾上腺素再摄取阻断特性形成对比。这些结果增加了一种可能性，即文拉法辛在体内对5-HT和去甲肾上腺素再摄取的作用可能不仅仅是通过其与[3H]氰米帕明和[3H]去甲替林结合位点的结合来介导的。
