Physiological Roles and Potential Therapeutic Applications of the P2X7 Receptor in Inflammation and Pain
Abstract
:1. Introduction
2. The P2X Family and the P2X7 Subtype
3. P2X7 Receptor Pharmacology
4. The Role of P2X7R in Inflammation
5. The Roles of P2X7 Receptors in Pain Disorders
5.1. Inflammatory Pain
5.2. Neuropathic Pain
Pain Model | Knockout Used | Experimental Context | Observed Effect | Reference |
---|---|---|---|---|
Inflammatory | P2X7R(-/-) | Fever by LPS or IL-1β intraperitoneal inoculation | Decreased febrile response in knockout mice | [119] |
Bone cancer pain | P2X7R(-/-) | Inoculation with 4T1 mammary cancer cells or NCTC 2472 osteosarcoma cells | No defects in bone cancer pain, probably related to P2X7 receptor splice variants expressed in the knockout mice | [118] |
Inflammatory and neuropathic | P2X7R(-/-) | Inflammatory (in an adjuvant-induced model) and neuropathic (in a partial nerve ligation model | Abolished pain sensitivity in both pain models | [65] |
6. P2X7 Receptor as a Novel Therapeutic Target
Compound | Company | Study | Trial Phase | Completed | Observed Result | Observed Side Effect | Reference |
---|---|---|---|---|---|---|---|
A-438079 | Abbott Laboratories | Neuropathic and inflammatory pain | Pre-clinical | Yes | Inhibited mechanical allodynia and effective in the formalin pain model | Not evaluated | [114] |
A-740003 | Abbott Laboratories | Neuropathic and inflammatory pain | Pre-clinical | Yes | Analgesic effect in inflammatory and neuropathic pain in rat | Not evaluated | [52] |
A804598 | Abbott Laboratories | Neuropathic and inflammatory pain | Pre-clinical | Yes | Analgesic effect in inflammatory and neuropathic pain in rat | Not evaluated | [25] |
A847227 | Abbott Laboratories | Anti-inflammatory and neuropathic pain | Pre-clinical | Yes | Antiallodynic activity and reduced the release of IL-1β in the zymosan mouse model | Not evaluated | [55] |
AZ10606120 | AstraZeneca | Ligand interaction and binding with P2X7R | Pre-clinical | Yes | Its molecule binds to a site different from which ATP binds, but it acts as a negative allosteric modulator | Not evaluated | [25] |
AZ11645373 | AstraZeneca | Selective potency | Pre-clinical | Yes | Inhibited hP2X7R and its pharmacologic properties | Not evaluated | [53] |
AZD9056 | AstraZeneca | Rheumatoid arthritis | II | Yes | No efficacy | Gastrointestinal (nausea, diarrhea, and vomiting) | [84] |
CE-224,835 | Pfizer | Rheumatoid arthritis | II | Yes | No efficacy | Gastrointestinal (nausea and diarrhea) | [83] |
EVT-401 | Evotec | The pharmacokinetic profile and pharmacodynamic effects | I | Yes | Safe and well tolerated | Not related | [78] |
GSK314118A | Glaxo | Inflammatory pain | Pre-clinical | Yes | Analgesic activity in rat CFA model of inflammatory hyperalgesia | Not related | [55] |
7. Conclusions
Acknowledgments
Conflicts of Interest
References
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Alves, L.A.; Bezerra, R.J.S.; Faria, R.X.; Ferreira, L.G.B.; Da Silva Frutuoso, V. Physiological Roles and Potential Therapeutic Applications of the P2X7 Receptor in Inflammation and Pain. Molecules 2013, 18, 10953-10972. https://doi.org/10.3390/molecules180910953
Alves LA, Bezerra RJS, Faria RX, Ferreira LGB, Da Silva Frutuoso V. Physiological Roles and Potential Therapeutic Applications of the P2X7 Receptor in Inflammation and Pain. Molecules. 2013; 18(9):10953-10972. https://doi.org/10.3390/molecules180910953
Chicago/Turabian StyleAlves, Luiz Anastacio, Rômulo José Soares Bezerra, Robson Xavier Faria, Leonardo Gomes Braga Ferreira, and Valber Da Silva Frutuoso. 2013. "Physiological Roles and Potential Therapeutic Applications of the P2X7 Receptor in Inflammation and Pain" Molecules 18, no. 9: 10953-10972. https://doi.org/10.3390/molecules180910953