Manias B, Taylor D A
Eur J Pharmacol. 1983 Nov 25;95(3-4):305-9. doi: 10.1016/0014-2999(83)90652-0.
The effects of in vivo administration of a number of antidepressants in doses up to 30 mg/kg i.p. on the in vitro uptake of 3H-amines were determined. The uptake of noradrenaline (NA) was competitively inhibited by 50% by desipramine, nomifensine and clomipramine. Dopamine uptake in the corpus striatum was inhibited by 50% by nomifensine. The uptake of 5-hydroxytryptamine (5-HT) was inhibited by clomipramine and fluoxetine. Iprindole and mianserin did not inhibit NA, DA or 5-HT uptake by more than 20%. The results demonstrate that the selectivities and potencies of antidepressants may be different in vivo to those in vitro. Thus, care should be taken when extrapolating to in vivo experiments, selectivities and potencies obtained in vitro.
测定了腹腔注射剂量高达30mg/kg的多种抗抑郁药对体外3H-胺摄取的影响。去甲丙咪嗪、诺米芬辛和氯米帕明对去甲肾上腺素(NA)的摄取有50%的竞争性抑制作用。诺米芬辛对纹状体中多巴胺的摄取有50%的抑制作用。氯米帕明和氟西汀对5-羟色胺(5-HT)的摄取有抑制作用。茚满丙二胺和米安色林对NA、DA或5-HT摄取的抑制作用不超过20%。结果表明,抗抑郁药在体内的选择性和效力可能与体外不同。因此,在将体外获得的选择性和效力外推至体内实验时应谨慎。