Buus Lassen J, Lund J, Bechgaard E, Søndergaard I
Psychopharmacology (Berl). 1979 Aug 8;64(2):149-53. doi: 10.1007/BF00496055.
A single treatment with 5-HT uptake inhibitors potentiates the hypermotility in mice produced by the MAO-inhibitor nialamide. The effect of nialamide on motility was studied in mice after 4 weeks of feeding with a normal diet and diets containing various concentrations of the 5-HT uptake inhibitors chlorimipramine and femoxetine. Chronic treatment with the two substances enhanced the motor effects of nialamide about equally, which indicates a preservation of the neuronal 5-HT uptake inhibition during such treatment. The effect of chlorimipramine and femoxetine was obtained at plasma levels equivalent to or lower than the steady-state plasma concentrations found in patients treated with two 5-HT uptake inhibitors. Determination of decreased blood 5-HT after the 4 weeks of treatment was used as an in vivo test for inhibition of 5-HT uptake into platelets. Femoxetine was a much weaker depletor of blood 5-HT than chlorimipramine. These results indicate that blockade of neuronal 5-HT uptake is obtained at lower doses of femoxetine than blockade of 5-HT uptake into platelets. In contrast, chlorimipramine presumably inhibits 5-HT uptake into neurons and platelets at about the same dose.
单次给予5-羟色胺（5-HT）摄取抑制剂可增强单胺氧化酶（MAO）抑制剂尼亚酰胺在小鼠中所产生的运动亢进。在用正常饮食以及含有不同浓度的5-HT摄取抑制剂氯米帕明和氟西汀的饮食喂养小鼠4周后，研究了尼亚酰胺对其运动的影响。长期使用这两种物质进行治疗对尼亚酰胺运动效应的增强作用大致相同，这表明在这种治疗过程中神经元5-HT摄取抑制作用得以保留。氯米帕明和氟西汀在等同于或低于接受两种5-HT摄取抑制剂治疗的患者体内稳态血药浓度的血浆水平时即可产生效应。在治疗4周后测定血液中5-HT的减少情况，以此作为体内检测血小板对5-HT摄取抑制作用的试验。氟西汀使血液中5-HT减少的作用比氯米帕明弱得多。这些结果表明，与抑制血小板摄取5-HT相比，较低剂量的氟西汀即可实现对神经元5-HT摄取的阻断。相反，氯米帕明大概在相同剂量时抑制5-HT向神经元和血小板的摄取。
