How does pindolol improve antidepressant action?
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.
Artigas
F
F
Dept of Neurochemistry, Institut d'Investigacions Biomèdiques de Barcelona (CSIC-IDIBAPS) Rosselló 161, 08036 Barcelona, Spain. fapnqi@iibb.csic.es
Celada
P
P
Laruelle
M
M
Adell
A
A
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D010869:Pindolol / Q000494:pharmacology / Q000627:therapeutic use*; D011985:Receptors, Serotonin / Q000187:drug effects; D017366:Serotonin Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use*
D000319:Adrenergic beta-Antagonists; D000928:Antidepressive Agents; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D010869:Pindolol