Artigas F, Romero L, de Montigny C, Blier P
Dept of Neurochemistry Instituto de Investigaciones Biomédicas de Barcelona (CSIC), Spain.
Trends Neurosci. 1996 Sep;19(9):378-83. doi: 10.1016/S0166-2236(96)10037-0.
At clinically relevant doses, selective serotonin (5-HT) reuptake inhibitors (SSRIs) and MAO inhibitors (MAOIs) increase the extracellular concentration of 5-HT in the midbrain raphé nuclei, thereby activating inhibitory somatodendritic 5-HT1A autoreceptors. Consequently, the firing activity of 5-HT neurons is reduced and the enhancement of extracellular 5-HT concentration in forebrain is dampened. Overriding this feedback by using antagonists of 5-HT1A autoreceptors permits SSRIs to produce a marked increase of extracellular 5-HT in the forebrain. Hence, combined treatment with an SSRI and a 5-HT1A antagonist increases the extracellular concentration of 5-HT more so than the former drug alone. The treatment of patients with major depression using an SSRI and pindolol, a 5-HT1A/ beta-adrenoceptor antagonist, markedly reduced the latency of the antidepressant response in previously untreated patients and induced a rapid improvement in treatment-resistant patients.
在临床相关剂量下，选择性5-羟色胺（5-HT）再摄取抑制剂（SSRIs）和单胺氧化酶抑制剂（MAOIs）会增加中脑缝际核中5-HT的细胞外浓度，从而激活抑制性的躯体树突状5-HT1A自身受体。因此，5-HT神经元的放电活动会降低，前脑中细胞外5-HT浓度的增强也会受到抑制。通过使用5-HT1A自身受体拮抗剂来克服这种反馈，可使SSRIs在前脑中显著增加细胞外5-HT。因此，与单独使用前一种药物相比，联合使用SSRI和5-HT1A拮抗剂可使细胞外5-HT浓度升高得更多。使用SSRI和5-HT1A/β-肾上腺素能受体拮抗剂哌哚洛尔治疗重度抑郁症患者，可显著缩短此前未接受治疗患者的抗抑郁反应潜伏期，并使难治性患者迅速改善。
