Artigas F, Celada P, Laruelle M, Adell A
Dept of Neurochemistry, Institut d'Investigacions Biomèdiques de Barcelona (CSIC-IDIBAPS) Rosselló 161, 08036 Barcelona, Spain.
Trends Pharmacol Sci. 2001 May;22(5):224-8. doi: 10.1016/s0165-6147(00)01682-5.
Since 1994, the beta-adrenoceptor and 5-HT(1A/1B) receptor ligand pindolol has been used to accelerate or enhance the clinical effects of antidepressant drugs, such as the selective 5-HT reuptake inhibitors (SSRIs), that act primarily on 5-HT-containing neurones. Pindolol was initially thought to act by preventing the inhibition of 5-HT release, elicited by SSRIs and other 5-HT-acting drugs, as a result of its ability to antagonize the action of 5-HT at midbrain raphe 5-HT(1A) autoreceptors that control the activity of ascending 5-HT-mediated pathways. However, the partial agonist properties of pindolol at 5-HT(1A) receptors and beta-adrenoceptors suggest that other explanations for its action are also possible. In this article, recent controversial data on the mechanism of action of pindolol, which are crucial for the development of more rapid and efficient antidepressant therapies, will be discussed.
自1994年以来，β-肾上腺素能受体和5-羟色胺（5-HT）（1A/1B）受体配体吲哚洛尔已被用于加速或增强抗抑郁药物的临床疗效，这些抗抑郁药物主要作用于含5-羟色胺的神经元，如选择性5-羟色胺再摄取抑制剂（SSRI）。最初认为，吲哚洛尔的作用机制是通过拮抗5-羟色胺对中脑缝际5-HT（1A）自身受体的作用，从而防止SSRI和其他作用于5-羟色胺的药物引起的5-羟色胺释放抑制，而中脑缝际5-HT（1A）自身受体可控制5-羟色胺介导的上行通路的活性。然而，吲哚洛尔在5-HT（1A）受体和β-肾上腺素能受体上具有部分激动剂特性，这表明其作用机制也可能有其他解释。本文将讨论关于吲哚洛尔作用机制的近期有争议的数据，这些数据对于开发更快速有效的抗抑郁疗法至关重要。
