Blockage of 5HT(2C) serotonin receptors by fluoxetine (Prozac)
Blockage of 5HT(2C) serotonin receptors by fluoxetine (Prozac)
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DOI：
10.1073/pnas.94.5.2036
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发表时间：
1997-03-04
影响因子：
11.1
通讯作者：
Miledi, R
中科院分区：
文献类型：
--
作者：
Ni, YG;Miledi, R
氟西汀（百忧解）抑制5-羟色胺引起的膜电流（5-羟色胺; 5 HT），由nM浓度的5 HT引起的5 HT（2C）受体的反应被微摩尔浓度的氟西汀快速可逆地阻断。对于由1 μ M 5 HT引起的反应，氟西汀抑制IC 50约为20 μ M。与电生理结果雅阁，氟西汀抑制[H-3] 5 HT与HeLa细胞中表达的5 HT（2C）受体的结合（Ki约为65-97 nM），并且与大鼠皮层膜中的5 HT受体的结合也被抑制，但效果较差（Ki约为56 μ M）。我们的研究结果表明氟西汀是一种竞争性的、可逆的5 HT（2C）受体拮抗剂，并提示氟西汀的某些治疗作用除了已知的5 HT转运体阻断作用外，还可能涉及5 HT受体的阻断作用。类似的工作可能有助于设计更有选择性的化合物用于治疗脑疾病。
Fluoxetine (Prozac) inhibited the membrane currents elicited by serotonin (5-hydroxytryptamine; 5HT) in Xenopus oocytes expressing either cloned 5HT(2C) receptors or 5HT receptors encoded by rat cortex mRNA, Responses of 5HT(2C) receptors, elicited by nM concentrations of 5HT, were rapidly and reversibly blocked by micromolar concentrations of fluoxetine, For responses elicited by 1 mu M 5HT, the IC50 Of fluoxetine inhibition was approximate to 20 mu M. In accord with the electrophysiological results, fluoxetine inhibited the binding of [H-3]5HT to 5HT(2C) receptors expressed in HeLa cells (K-i approximate to 65-97 nM), and the binding to 5HT receptors in rat cortex membranes was also inhibited but less efficiently (K-i approximate to 56 mu M). Our results show that fluoxetine is a competitive and reversible antagonist of 5HT(2C) receptors and suggest that some therapeutic effects of fluoxetine may involve blockage of 5HT receptors, in addition to its known blockage of 5HT transporters, Similar work may help to design more selective compounds for use in the treatment of brain disorders.