Delayed pharmacological effects of antidepressants
Delayed pharmacological effects of antidepressants
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DOI：
10.1038/sj.mp.4001015
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发表时间：
2002-01-01
影响因子：
11
通讯作者：
Benmansour, S
中科院分区：
文献类型：
--
作者：
Frazer, A;Benmansour, S
尽管抗抑郁药可能不是主要的情绪稳定剂，但它们在预防反复发作的抑郁症以及治疗急性发作方面是有效的。可能有助于这些药物预防作用的药理作用尚不清楚。已经开展的研究中，给实验动物(如大鼠)服用抗抑郁药的时间长达3-4周。在这类研究中获得的数据被认为对它们在抑郁发作中的有益作用很重要，但也可能与它们的预防作用有关。结果表明，当给予5-羟色胺或去甲肾上腺素摄取的选择性抑制剂时，它们仍然对5-羟色胺或去甲肾上腺素能参数产生选择性影响。例如，长期服用选择性去甲肾上腺素再摄取抑制剂会导致β(1)肾上腺素受体的下调。选择性5-羟色胺再摄取抑制剂不会产生这种效果。长期服用选择性5-羟色胺再摄取抑制剂会导致5-羟色胺转运体的下调，但不会导致去甲肾上腺素转运体的下调。相比之下，选择性去甲肾上腺素再摄取抑制剂下调去甲肾上腺素转运体，但不下调5-羟色胺转运体。5-羟色胺转运体结合部位的大量丢失需要15天才能发生，并伴随着体内5-羟色胺转运体功能的显著降低。
Although antidepressants may not be primary mood stabilizers, they are efficacious in the prophylaxis of recurrent depressive illnesses, as well as in the treatment of acute episodes. Pharmacological effects that may contribute to the prophylactic effects of these drugs are not understood. Studies have been carried out in which antidepressants have been given to laboratory animals, such as rats, for periods of up to 3-4 weeks. Data obtained in such studies are thought to be important for their beneficial effects in depressive episodes, but also may be relevant to their prophylactic effects. Results are presented showing that when selective inhibitors of serotonin or norepinephrine uptake are given for such time periods, they still produce selective effects on serotonergic or noradrenergic parameters. For example, long-term administration of selective norepinephrine reuptake inhibitors causes a down-regulation of beta(1) adrenoceptors. Selective serotonin reuptake inhibitors do not produce this effect. Longterm administration of selective serotonin reuptake inhibitors causes down-regulation of the serotonin transporter, but not the norepinephrine transporter. In contrast, selective norepinephrine reuptake inhibitors down-regulate the norepinephrine transporter but not the serotonin transporter. Substantial loss of serotonin transporter binding sites takes 15 days to occur and is accompanied by a marked reduction of serotonin transporter function in vivo.