Diggory G L, Stephens R J, Dickison S E, Moser P, Wood M D
Arch Int Pharmacodyn Ther. 1980 Nov;248(1):86-104.
Wy 25093 is a novel, selective and potent inhibitor of the neuronal 5-hydroxytryptamine (5-HT) uptake process in vitro and in vivo. The compound was more potent than clomipramine and fluoxetine as an inhibitor of 5-HT uptake in vitro and did not significantly inhibit catecholamine uptake. In addition, Wy 25093 potentiated the behavioural syndrome induced by 5-hydroxytryptophan (5-HTP) and antagonised the hyperactivity produced by p-chloroamphetamine (P-CA). WY 25093 antagonised the (P-CA)-induced depletion of 5-HT in rat brain and reduced the probenecid-induced increase in rat brain 5-hydroxyindole-3-acetic acid (5-HIAA). Acute administration of the agent to rats resulted in reduced 5-HIAA levels without affecting 5-HT; chronic treatment with the compound produced decreases in the levels of both 5-HIAA and 5-HT. It is concluded that Wy 25093 is a selective and potent inhibitor of the neuronal re-uptake process for 5-HT both in vitro and in vivo, and may possess potential antidepressant activity.
Wy 25093是一种新型、具有选择性且强效的神经元5-羟色胺（5-HT）摄取过程抑制剂，在体外和体内均有此作用。作为5-HT摄取的抑制剂，该化合物在体外比氯米帕明和氟西汀更有效，且对儿茶酚胺摄取无明显抑制作用。此外，Wy 25093增强了5-羟色氨酸（5-HTP）诱导的行为综合征，并拮抗了对氯苯丙胺（P-CA）产生的多动。WY 25093拮抗了（P-CA）诱导的大鼠脑内5-HT耗竭，并降低了丙磺舒诱导的大鼠脑内5-羟吲哚-3-乙酸（5-HIAA）升高。对大鼠急性给药该药物导致5-HIAA水平降低，但不影响5-HT；用该化合物长期治疗会使5-HIAA和5-HT水平均下降。结论是，Wy 25093在体外和体内均是5-HT神经元再摄取过程的选择性强效抑制剂，可能具有潜在的抗抑郁活性。
