Format

Send to

Choose Destination
Int J Mol Sci. 2015 Aug 7;16(8):18474-506. doi: 10.3390/ijms160818474.

Functional Selectivity and Antidepressant Activity of Serotonin 1A Receptor Ligands.

Author information

1
National Medicines Institute, Chełmska 30/34, 00-725 Warszawa, Poland. z.chilmonczyk@nil.gov.pl.
2
Institute of Nursing and Health Sciences, University of Rzeszów, W. Kopisto 2A, 35-310 Rzeszów, Poland. z.chilmonczyk@nil.gov.pl.
3
Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Kraków, Poland. bojarski@if-pan.krakow.pl.
4
Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Kraków, Poland. nfpilc@cyf-kr.edu.pl.
5
Faculty of Health Sciences, University of Tromsø-The Arctic University of Norway, No-9037 Tromsø, Norway. ingebrigt.sylte@uit.no.

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.

KEYWORDS:

antidepressant activity; receptor trafficking; serotonin 1A receptors

PMID:
26262615
PMCID:
PMC4581256
DOI:
10.3390/ijms160818474
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Multidisciplinary Digital Publishing Institute (MDPI) Icon for PubMed Central
Loading ...
Support Center