Abstract
Antidepressant use has resulted in a variety of negative consequences, including permanent brain damage and erectile dysfunction. So, the purpose lies in develo** something more productive with minimal side effects and consequently improved efficacy. A growing body of evidences indicated a remarkable purinergic signalling system, which helped in dealing with this complication. This has been found to be a powerful formula in dealing with psychiatric disorders. P1 (adenosine), P2X, and P2Y (ATP) are the receptors, involved in the pathology as well as exhibiting the therapeutic action by triggering the purinergic pathway. It was found that A2A and P2X7 receptors specifically were involved and recognized as possible targets for treating depression. Further, the development of biomarkers for the diagnosis of depression has also been attributed to accelerate the process. One such biomarker includes serum uric acid. Many clinical studies reveal the importance of antagonizing P2X7 and A2A receptors, for promising research in understanding the molecular premises of depression. However, further investigations are still needed to be done to open several unfolded mysteries for a better and safe upshot. The selective antagonists for A2A and P2X7 receptors may have antidepressant effects showing positive results, in agreement with non-clinical testing. In this review, efforts are being devoted to the targeted receptors in bringing out antidepressant effects with a possible link involving depression and defined purinergic signalling. Additionally, the overview of various receptors, including their functions and distribution, is being explored in a representative way along with the biomarkers involved.
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Abbreviations
- ATP:
-
Adenosine triphosphate
- AMP:
-
Adenosine monophosphate
- ADO:
-
Adenosine
- GPCR:
-
G-protein-coupled receptor
- GABA:
-
Gama-aminobutyric acid
- ADP:
-
Adenosine diphosphate
- UTP:
-
Uridine-5′-triphosphate
- UDP:
-
Uridine-5′-diphosphate
- NO:
-
Nitric oxide
- IBD:
-
Inflammatory bowel disease
- TME:
-
Tumour microenvironment
- GMP:
-
Guanosine monophosphate
- IP3:
-
Inositol triphosphate
- OXPHOS:
-
Oxidative phosphorylation
- IL-6:
-
Interleukin-6
- ROS:
-
Reactive oxygen species
- IMP:
-
Inosine monophosphate
- cAMP:
-
Cyclic adenosine monophosphate
- PLC:
-
Phospholipase C
- 5-HT:
-
5-Hydroxytriptamine
- DAMP:
-
Damage-associated molecular patterns
- SSRi:
-
Selective serotonin reuptake inhibitor
- SNRi:
-
Selective norepinephrine reuptake inhibitors
- CRP:
-
C-reactive protein
- TNF-α:
-
Tumor necrosis factor-α
- PYD:
-
Pyridinoline
- IL-Ib:
-
Interleukin-1 beta
- BDNF:
-
Brain-derived neurotrophic factor
- NA:
-
Nor-adrenaline
- GLAST:
-
Glutamate sodium-dependent transporter
- PAMP:
-
Pathogen associated molecular patterns
- PRP:
-
Pattern recognition receptors
- NOD:
-
Nucleotide-binding oligomerisation
- IFN-γ:
-
Interferon-gamma
- TCA:
-
Tricyclic antidepressants
- SVZ:
-
Subventricular zone
- VEGF:
-
Vascular endothelial growth factor
- MAOI:
-
Monoamine oxidase inhibitors
- XO:
-
Xanthine oxidase
- PNP:
-
Purine nucleoside phosphorylase
- SUA:
-
Serum uric acid
- MDD:
-
Major depressive disorder
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The authors would like to thank Chitkara College of Pharmacy, Chitkara University, Punjab, India, for providing basic resources for the completion of the current article.
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Sikka, P., Behl, T., Chandel, P. et al. Scrutinizing the Therapeutic Promise of Purinergic Receptors Targeting Depression. Neurotox Res 40, 1570–1585 (2022). https://doi.org/10.1007/s12640-022-00550-2
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DOI: https://doi.org/10.1007/s12640-022-00550-2