Delayed pharmacological effects of antidepressants

被引:119
作者
Frazer, A
Benmansour, S
机构
[1] Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78229 USA
[2] Audie L Murphy Mem Hosp, S Texas Vet Hlth Care Syst, San Antonio, TX USA
关键词
selective serotonin reuptake inhibitors; selective norepinephrine reuptake inhibitors; serotonin transporter; norepinephrine transporter;
D O I
10.1038/sj.mp.4001015
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:S23 / S28
页数:6
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