Serotonin transporter and receptor ligands with antidepressant activity as neuroprotective and proapoptotic agents.
Serotonin exhibits multiple non-neural functions involved in essential hypertension, early embryogenesis, follicle maturation and behaviour. The growth stimulatory effects of the neurotransmitter have been described for a variety of cell types. 5-HT was found to induce migration of the human prostate cancer cell lines - PC-3 and Du145 - and several 5-HT1Aantagonists and serotonin reuptake inhibitors were reported to inhibit the growth of different tumour cell lines in vitro. Recent studies suggest that neurogenesis is involved in the action of antidepressants and an involvement of antidepressants in adult hippocampal neurogenesis has been demonstrated. Antidepressants also exhibit neuroprotective activity, which could be connected to their antidepressant activity. However, it has been reported that certain antidepressants may induce apoptosis in some cancer cell lines. In the present paper the neuroprotective and proapoptotic activities of serotonergic antidepressants (SSRIs and TCAs), as well as 5-HT1Areceptor ligands are summarized and discussed based on biochemical transduction pathways associated with these activities.
National Medicines Institute, Warszawa, Poland. Electronic address: z.chilmonczyk@nil.gov.pl.
Zdzislaw
Z
Chilmonczyk
Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
Andrzej J
AJ
Bojarski
Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
Andrzej
A
Pilc
Department of Medical Biology, Faculty of Health Sciences, UiT - The Arctic University of Norway, Tromsø, Norway.
Ingebrigt
I
Sylte
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D006801:Humans; D008024:Ligands; D018696:Neuroprotective Agents / Q000494:pharmacology*; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
D000928:Antidepressive Agents; D008024:Ligands; D018696:Neuroprotective Agents; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors
Apoptosis; Neuroprotection; Serotonin ligands