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Functional selectivity and antidepressant activity of serotonin 1A receptor ligands

Permanent link
https://hdl.handle.net/10037/8819
DOI
https://doi.org/10.3390/ijms160818474
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Date
2015
Type
Journal article
Tidsskriftartikkel
Peer reviewed

Author
Chilmonczyk, Zdzislaw; Bojarski, Andrzej Jacek; Pilc, Andrzej; Sylte, Ingebrigt
Abstract
Serotonin (5-HT) is a monoamine neurotransmitter that plays an important role in physiological functions. 5-HT has been implicated in sleep, feeding, sexual behavior, temperature regulation, pain, and cognition as well as in pathological states including disorders connected to mood, anxiety, psychosis and pain. 5-HT1A receptors have for a long time been considered as an interesting target for the action of antidepressant drugs. It was postulated that postsynaptic 5-HT1A agonists could form a new class of antidepressant drugs, and mixed 5-HT1A receptor ligands/serotonin transporter (SERT) inhibitors seem to possess an interesting pharmacological profile. It should, however, be noted that 5-HT1A receptors can activate several different biochemical pathways and signal through both G protein-dependent and G protein-independent pathways. The variables that affect the multiplicity of 5-HT1A receptor signaling pathways would thus result from the summation of effects specific to the host cell milieu. Moreover, receptor trafficking appears different at pre- and postsynaptic sites. It should also be noted that the 5-HT1A receptor cooperates with other signal transduction systems (like the 5-HT1B or 5-HT2A/2B/2C receptors, the GABAergic and the glutaminergic systems), which also contribute to its antidepressant and/or anxiolytic activity. Thus identifying brain specific molecular targets for 5-HT1A receptor ligands may result in a better targeting, raising a hope for more effective medicines for various pathologies.
Description
Published version. Source at http://doi.org/10.3390/ijms160818474.
Publisher
MDPI
Citation
International Journal of Molecular Sciences 2015, 16(8):18474-18506
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