Functional Selectivity and Antidepressant Activity of Serotonin 1A Receptor Ligands

International Journal of Molecular Sciences

Zdzisᐪw Chilmonczyk¹  Andrzej Jacek Bojarski²  Andrzej Pilc²  Ingebrigt Sylte³ 

[1] National Medicines Institute, Chełmska 30/34, 00-725 Warszawa, Poland;Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Kraków, Poland; E-Mails:;Faculty of Health Sciences, University of Tromsø—The Arctic University of Norway, No-9037 Tromsø, Norway; E-Mail:

关键词: serotonin 1A receptors;    receptor trafficking;    antidepressant activity;   

DOI  :  10.3390/ijms160818474

来源: mdpi

【 摘 要 】

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-HT_1A receptors have for a long time been considered as an interesting target for the action of antidepressant drugs. It was postulated that postsynaptic 5-HT_1A agonists could form a new class of antidepressant drugs, and mixed 5-HT_1A receptor ligands/serotonin transporter (SERT) inhibitors seem to possess an interesting pharmacological profile. It should, however, be noted that 5-HT_1A 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-HT_1A 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-HT_1A receptor cooperates with other signal transduction systems (like the 5-HT_1B or 5-HT_2A/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-HT_1A receptor ligands may result in a better targeting, raising a hope for more effective medicines for various pathologies.

【 授权许可】

CC BY   
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