氟西汀（百忧解）对5HT2C血清素受体的阻断作用。
Blockage of 5HT2C serotonin receptors by fluoxetine (Prozac).
作者信息
Ni Y G, Miledi R
机构信息
Department of Psychobiology, University of California, Irvine 92697-4550, USA.
出版信息
Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):2036-40. doi: 10.1073/pnas.94.5.2036.
Fluoxetine (Prozac) inhibited the membrane currents elicited by serotonin (5-hydroxytryptamine; 5HT) in Xenopus oocytes expressing either cloned 5HT2C receptors or 5HT receptors encoded by rat cortex mRNA. Responses of 5HT2C receptors, elicited by nM concentrations of 5HT, were rapidly and reversibly blocked by micromolar concentrations of fluoxetine. For responses elicited by 1 microM 5HT, the IC50 of fluoxetine inhibition was approximately 20 microM. In accord with the electrophysiological results, fluoxetine inhibited the binding of [3H]5HT to 5HT2C receptors expressed in HeLa cells (Ki approximately 65-97 nM), and the binding to 5HT receptors in rat cortex membranes was also inhibited but less efficiently (Ki approximately 56 microM). Our results show that fluoxetine is a competitive and reversible antagonist of 5HT2C 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.
氟西汀（百忧解）抑制了在表达克隆的5HT2C受体或大鼠皮质mRNA编码的5HT受体的非洲爪蟾卵母细胞中，血清素（5-羟色胺；5HT）引发的膜电流。由纳摩尔浓度的5HT引发的5HT2C受体反应，被微摩尔浓度的氟西汀迅速且可逆地阻断。对于由1微摩尔5HT引发的反应，氟西汀抑制的IC50约为20微摩尔。与电生理结果一致，氟西汀抑制了[3H]5HT与HeLa细胞中表达的5HT2C受体的结合（Ki约为65 - 97纳摩尔），并且对大鼠皮质膜中5HT受体的结合也有抑制作用，但效率较低（Ki约为56微摩尔）。我们的结果表明，氟西汀是5HT2C受体的竞争性可逆拮抗剂，并表明氟西汀的一些治疗作用可能除了其已知的对5HT转运体的阻断作用外，还涉及对5HT受体的阻断。类似的研究可能有助于设计更具选择性的化合物用于治疗脑部疾病。
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