Roberts Claire, Hagan Jim J, Bartoszyk Gerd D, Kew James N C
Psychiatry CEDD, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex, CM19 5AW, United Kingdom.
Eur J Pharmacol. 2005 Jul 4;517(1-2):59-63. doi: 10.1016/j.ejphar.2005.05.039.
The effect of vilazodone, a putative selective serotonin re-uptake inhibitor (SSRI) with 5-HT (5-hydroxytryptamine)(1A) receptor partial agonist activity, was investigated on 5-HT efflux and 5-HT re-uptake half life in the guinea-pig dorsal raphe nucleus, using in vitro fast cyclic voltammetry. The SSRI, fluoxetine, significantly increased 5-HT efflux. In contrast, vilazodone had no effect on 5-HT efflux at 100 nM but significantly decreased 5-HT efflux at 1 microM. Co-perfusion of 8-OH-DPAT (+/-8-hydroxy-2-(di-n-propylamino)tetralin) with fluoxetine significantly attenuated the fluoxetine-induced increase in 5-HT efflux. Co-perfusion of WAY 100635 with vilazodone did not attenuate the effect of vilazodone alone. In addition, the re-uptake half life for 5-HT was significantly increased by both fluoxetine and vilazodone. In conclusion, we have demonstrated that vilazodone (100 nM, 1 microM), in the guinea-pig dorsal raphe nucleus, blocks the serotonin transporter but does not display 5-HT(1A) receptor agonism.
维拉佐酮是一种被认为具有5-羟色胺（5-HT）（1A）受体部分激动剂活性的选择性5-羟色胺再摄取抑制剂（SSRI），本研究使用体外快速循环伏安法，研究了其对豚鼠中缝背核5-HT流出及5-HT再摄取半衰期的影响。SSRI氟西汀可显著增加5-HT流出。相比之下，维拉佐酮在100 nM时对5-HT流出无影响，但在1 μM时可显著降低5-HT流出。8-OH-DPAT（±8-羟基-2-（二正丙基氨基）四氢萘）与氟西汀共同灌注可显著减弱氟西汀诱导的5-HT流出增加。WAY 100635与维拉佐酮共同灌注并未减弱维拉佐酮单独的作用。此外，氟西汀和维拉佐酮均可显著增加5-HT的再摄取半衰期。总之，我们已证明，在豚鼠中缝背核中，维拉佐酮（100 nM，1 μM）可阻断5-羟色胺转运体，但不表现出5-HT（1A）受体激动作用。
