Greenwood D T, Kemp J D, Middlemiss D N
J Pharm Pharmacol. 1982 Jan;34(1):38-41. doi: 10.1111/j.2042-7158.1982.tb04674.x.
The effects of the antidepressant drug viloxazine and its two optically active isomers on the passive avoidance learning deficit surgically induced in rats by bilateral bulbectomy have been determined. Fourteen consecutive daily injections of either the racemate or the S-isomer (2, 5 and 10 mg kg-1 i.p.) significantly improved the acquisition of avoidance behaviour. The R-isomer was devoid of such activity in this same dose range. The various isomeric species of viloxazine were also studied in vitro for their ability to induce a release of noradrenaline, dopamine and 5-hydroxytryptamine (5-HT) from rat brain slices. In agreement with previous reports, racemic viloxazine caused a concentration-dependent (10(-5)-10(-3 M) release of 5-MT without affecting any significant change in the release of either catecholamine. However, in contrast to the results of the behavioural studies, this phenomenon did not exhibit stereospecificity, all three isomeric forms being equally active. Thus, there is no simple relationship between viloxazine's behavioural activity in bulbectomized rats and its 5-HT releasing properties observed in vitro. The significance of these findings with respect to previously reported effects of the drug indicative of facilitation of central 5-HT mediated processes is discussed.
已确定抗抑郁药维洛沙嗪及其两种旋光异构体对双侧延髓切除术手术诱导的大鼠被动回避学习缺陷的影响。连续14天每天腹腔注射消旋体或S - 异构体（2、5和10 mg·kg⁻¹）可显著改善回避行为的习得。在相同剂量范围内，R - 异构体没有这种活性。还在体外研究了维洛沙嗪的各种异构体诱导大鼠脑片释放去甲肾上腺素、多巴胺和5 - 羟色胺（5 - HT）的能力。与先前的报道一致，消旋维洛沙嗪引起5 - HT浓度依赖性（10⁻⁵ - 10⁻³ M）释放，而不影响任何一种儿茶酚胺释放的显著变化。然而，与行为学研究结果相反，这种现象没有表现出立体特异性，所有三种异构体形式的活性相同。因此，在延髓切除大鼠中维洛沙嗪的行为活性与其体外观察到的5 - HT释放特性之间没有简单的关系。讨论了这些发现对于先前报道的该药物表明促进中枢5 - HT介导过程的作用的意义。
