New therapeutic targets in the treatment of affective disorders, anxiety and depression

• Autorzy: Plaznik A.
• Języki publikacji: EN

Abstrakty

EN

I have selected problems that focus on innovative approaches rather than reviewing existing mechanisms and their well known limitations. Small molecules capable of blocking neuropeptide receptors have the potential to become novel antidepressants. Likely candidates have been corticotropin releasing factor CRF antagonists and neurokinin-1 receptor antagonists. However, the effi cacy of this treatment was not confi rmed in clinical phase III trials. Preclinical data from α2,3-subunit selective GABA-A receptor agonists suggest that these targets may yield anxioselective agents. However, the α1 subtype mediates a substantial proportion of the anxiolytic actions of benzodiazepines. Considering that GABA-A1 receptors are expressed in higher densities than GABA-A2 or -A3 receptors and that there is substantial overlap of their localization, it may remain necessary to have a residual degree of their activation to achieve clinically signifi cant anxiolysis. The discovery of novel molecules designed to regulate the specifi c aspects of neurogenesis may lead to improved CNS therapeutics, including antidepressant drugs. The majority of antidepressant drugs currently prescribed for the treatment of depression inhibits the reuptake of serotonin and/or norepinephrine. The strategy for developing triple reuptake inhibitors (TRIs) is based on preclinical and clinical studies indicating that adding a dopaminergic component will improve these therapies. Metabotropic glutamate receptors mGlu2,3 and mGlu5, and the cannabinoid receptors CB1 and CB2 are also attractive therapeutic targets. It is concluded, that a deeper understanding of the breadth of neuromodulators structural diversity as well as the components required for their stimulation/inhibition will guide a rational drug development.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2009
• Tom: 69
• Numer: 1
• Opis fizyczny: p.84

Twórcy

autor

Plaznik A.

• Department of Neurochemistry, Institute of Psychiatry and Neurology, Warsaw, Poland