Tatiana A. Gudasheva*, Polina Povarnina, Alexey V. Tarasiuk and Sergey B. Seredenin Pages 729 - 737 ( 9 )
The search for new highly-effective, fast-acting antidepressant drugs is extremely relevant. Brain derived neurotrophic factor (BDNF) and signaling through its tropomyosin-related tyrosine kinase B (TrkB) receptor, represents one of the most promising therapeutic targets for treating depression. BDNF is a key regulator of neuroplasticity in the hippocampus and the prefrontal cortex, the dysfunction of which is considered to be the main pathophysiological hallmark of this disorder. BDNF itself has no favorable drug-like properties due to poor pharmacokinetics and possible adverse effects. The design of small, proteolytically stable BDNF mimetics might provide a useful approach for the development of therapeutic agents. Two small molecule BDNF mimetics with antidepressant-like activity have been reported, 7,8-dihydroxyflavone and the dimeric dipeptide mimetic of BDNF loop 4, GSB-106. The article reflects on the current literature on the role of BDNF as a promising therapeutic target in the treatment of depression and on the current advances in the development of small molecules on the base of this neurotrophin as potential antidepressants.
BDNF, depression, dimeric dipeptide mimetic, GSB-106, 7,8-dihydroxyflavone, antidepressants.
Medicinal Chemistry Department, V.V. Zakusov Research Institute of Pharmacology, ul. Baltijskaya, 8, 124315 Moscow, Medicinal Chemistry Department, V.V. Zakusov Research Institute of Pharmacology, ul. Baltijskaya, 8, 124315 Moscow, Medicinal Chemistry Department, V.V. Zakusov Research Institute of Pharmacology, ul. Baltijskaya, 8, 124315 Moscow, Department of Pharmacogenetics, V.V. Zakusov Research Institute of Pharmacology, ul. Baltijskaya, 8, 124315 Moscow